Ivabradine Induces Cardiac Protection against Myocardial Infarction by Preventing Cyclophilin-A Secretion in Pigs under Coronary Ischemia/Reperfusion

In response to cardiac ischemia/reperfusion, proteolysis mediated by extracellular matrix metalloproteinase inducer (EMMPRIN) and its secreted ligand cyclophilin-A (CyPA) significantly contributes to cardiac injury and necrosis. Here, we aimed to investigate if, in addition to the effect on the funny current (I(f)), Ivabradine may also play a role against cardiac necrosis by reducing EMMPRIN/CyPA-mediated cardiac inflammation. In a porcine model of cardiac ischemia/reperfusion (IR), we found that administration of 0.3 mg/kg Ivabradine significantly improved cardiac function and reduced cardiac necrosis by day 7 after IR, detecting a significant increase in cardiac CyPA in the necrotic compared to the risk areas, which was inversely correlated with the levels of circulating CyPA detected in plasma samples from the same subjects. In testing whether Ivabradine may regulate the levels of CyPA, no changes in tissue CyPA were found in healthy pigs treated with 0.3 mg/kg Ivabradine, but interestingly, when analyzing the complex EMMPRIN/CyPA, rather high glycosylated EMMPRIN, which is required for EMMPRIN-mediated matrix metalloproteinase (MMP) activation and increased CyPA bonding to low-glycosylated forms of EMMPRIN were detected by day 7 after IR in pigs treated with Ivabradine. To study the mechanism by which Ivabradine may prevent secretion of CyPA, we first found that Ivabradine was time-dependent in inhibiting co-localization of CyPA with the granule exocytosis marker vesicle-associated membrane protein 1 (VAMP1). However, Ivabradine had no effect on mRNA expression nor in the proteasome and lysosome degradation of CyPA. In conclusion, our results point toward CyPA, its ligand EMMPRIN, and the complex CyPA/EMMPRIN as important targets of Ivabradine in cardiac protection against IR.     

Lipofilling in Breast Oncological Surgery: A Safe Opportunity or Risk for Cancer Recurrence?

Lipofilling (LF) is a largely employed technique in reconstructive and esthetic breast surgery. Over the years, it has demonstrated to be extremely useful for treatment of soft tissue defects after demolitive or conservative breast cancer surgery and different procedures have been developed to improve the survival of transplanted fat graft. The regenerative potential of LF is attributed to the multipotent stem cells found in large quantity in adipose tissue. However, a growing body of pre-clinical evidence shows that adipocytes and adipose-derived stromal cells may have pro-tumorigenic potential. Despite no clear indication from clinical studies has demonstrated an increased risk of cancer recurrence upon LF, these observations challenge the oncologic safety of the procedure. This review aims to provide an updated overview of both the clinical and the pre-clinical indications to the suitability and safety of LF in breast oncological surgery. Cellular and molecular players in the crosstalk between adipose tissue and cancer are described, and heterogeneous contradictory results are discussed, highlighting that important issues still remain to be solved to get a clear understanding of LF safety in breast cancer patients.     

Visceral Adipose Tissue Displays Unique Metabolomic Fingerprints in Obesity,Pre-Diabetes and Type 2 Diabetes

Visceral adipose tissue (VAT) metabolic profiling harbors the potential to disentangle molecular changes underlying obesity-related dysglycemia. In this study, the VAT exometabolome of subjects with obesity and different glycemic statuses are analyzed. The subjects (n = 19) are divided into groups according to body mass index and glycemic status: subjects with obesity and euglycemia (Ob+NGT, n = 5), subjects with obesity and pre-diabetes (Ob+Pre-T2D, n = 5), subjects with obesity and type 2 diabetes under metformin treatment (Ob+T2D, n = 5) and subjects without obesity and with euglycemia (Non-Ob, n = 4), used as controls. VATs are incubated in culture media and extracellular metabolite content is determined by proton nuclear magnetic resonance (¹H-NMR). Glucose consumption is not different between the groups. Pyruvate and pyroglutamate consumption are significantly lower in all groups of subjects with obesity compared to Non-Ob, and significantly lower in Ob+Pre-T2D as compared to Ob+NGT. In contrast, isoleucine consumption is significantly higher in all groups of subjects with obesity, particularly in Ob+Pre-T2D, compared to Non-Ob. Acetate production is also significantly lower in Ob+Pre-T2D compared to Non-Ob. In sum, the VAT metabolic fingerprint is associated with pre-diabetes and characterized by higher isoleucine consumption, accompanied by lower acetate production and pyruvate and pyroglutamate consumption. We propose that glucose metabolism follows different fates within the VAT, depending on the individuals’ health status.     

Investigation of the Anti-Methicillin-Resistant Staphylococcus aureus Activity of (+)-Tanikolide- and (+)-Malyngolide-Based Analogues Prepared by Asymmetric Synthesis

Herein, we report antibacterial and antifungal evaluation of a series of previously prepared (+)-tanikolide analogues. One analogue, (4S,6S)-4-methyltanikolide, displayed promising anti-methicillin-resistant Staphylococcus aureus activity with a MIC of 12.5 µg/mL. Based on the antimicrobial properties of the structurally related (−)-malyngolide, two further analogues (4S,6S)-4-methylmalyngolide and (4R,6S)-4-methylmalyngolide bearing a shortened n-nonyl alkyl side chain were prepared in the present study using a ZrCl₄-catalysed deprotection/cyclisation as the key step in their asymmetric synthesis. When these were tested for activity against anti-methicillin-resistant Staphylococcus aureus, the MIC increased to 50 µg/mL.     

Relation of swelling and Tg depression to the apparent free volume of a particle‐filled,epoxy‐based adhesive

The effect of hygrothermal aging on a particle‐filled, epoxy‐based adhesive was studied using a gravimetric sorption technique. This study has explored moisture sorption characteristics as well as the associated behaviors of swelling and the depression of the glass transition temperature (T_g). We observed that the diffusion of water in this adhesive has a non‐Fickian behavior, and the depression of T_g proceeds to a definite value that is independent of the final equilibrium water content of the system. Our observations suggest that water diffuses into the polymer in a dual‐sorption mode, in which water resides in two populations. In one population, water is considered to occupy apparent free volume of the adhesive, and the second population water infiltrates polymer structure and forms hydrogen‐bonded clusters. Our results show that hygrothermal aging temperature and swelling do not alter the apparent free volume of this adhesive. We conclude that the constant value of T_g depression at saturation implies that only water in the apparent free volume is responsible for the T_g depression, whereas the swelling proceeds through the formation of hydrogen bonds in the adhesive. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 87: 1436–1444, 2003     

Very long chain PUFA in murine testicular triglycerides and cholesterol esters

Very long chain (VLC) PUFA of the n−6 and n−3 series are known to occur in mammalian testis. The aim of this work was to characterize further two testicular lipid classes with VLCPUFA, cholesterol esters (CE) and total triglycerides (TG) in rat and mouse testis. The VLCPUFA predominating in these lipids were a series of n−6 pentaenes and tetraenes with 24 to 32 carbons, including small amounts of odd-chain PUFA, 28∶5n−6 and 24∶5n−6 prevailing in CE and TG, respectively. Most of the VLCPUFA of TG were concentrated in a small fraction of TG, made up by 1-O-alkyl-2,3-DAG. This TG subclass was absent altogether from the TG of sexually immature testis. The TG and the CE with VLCPUFA only occurred in testis of adult fertile animals. The proportion of VLCPUFA in total TG and CE was higher in rodents than in other mammals. In the n−6 PUFA-rich adult mouse testis, the amounts of testicular triacylglycerols decreased significantly after consumption of fish oil for 2 wk. Whereas 18∶2n−6 was significantly reduced, the amounts of 22∶5n−6 and longer n−6 PUFA were less affected in all mamor testicular lipids including PC and PE, where they were unchanged. The 1-O-alkyl-2,3-DAG and their n−6 VLCPUFA were virtually unaffected by the diet. The VLCPUFA-containing molecular species of CE and TG may represent a form of storage of cholesterol and polyenoic FA required to sustain spermatogenesis. Via chain-shortening, VLCPUFA stored in the neutral lipids may serve as precursors of the major C₂₂ PUFA typical of cell membrane glycerophospholipids, protecting testicular cells against shifts in FA composition induced by dietary changes.     

Selective separation of yttrium from rare earth elements by ion interaction chromatography. Analytical and larger scale applications

ABSTRACT

New ion interaction chromatographic (IIC) method employing Kromasil 100 C₁₈ column and tetra-n-butylammonium hydroxide (TBAOH) as an ion interaction reagent (IIR) is able to separate yttrium from Rare Earth Elements (REE) as anionic complexes with nitrilotriacetic acid (NTA). New method for the chromatographic determination of Y in REE mixture was devised and validated by the analysis of the certified reference material (CRM). Potential possibilities of the new chromatographic system for larger scale applications including macro-micro events were demonstrated.     

Pathways for fatty acid elongation and desaturation in Neurospora crassa

Neurospora crassa incorporated exogenous deuterated palmitate (16∶0) and ¹⁴C-labeled oleate (18∶1^Δ9) into cell lipids. Of the exogenous 18∶1^Δ9 incorporated, 59% was desaturated to 18∶2^Δ9,12 and 18∶3^Δ9,12,15. Of the exogenous 16∶0 incorporated, 20% was elongated to 18∶0, while 37% was elongated and desaturated into 18∶1^Δ9, 18∶2^Δ9,12, and 18∶3^Δ9,12,15. The mass of unsaturated fatty acids in phospholipid and triacylglycerol is 12 times greater than the mass of 18∶0. Deuterium label incorporation in unsaturated fatty acids is only twofold greater than in 18∶0, indicating a sixfold preferential use of 16∶0 for saturated fatty acid synthesis. These results indicate that the release of 16∶0 from fatty acid synthase is a key control point that influences fatty acid composition in Neurospora.     

Simple approach for the plasma treatment of polymeric membranes and investigation of the aging effect

The modification of the surface characteristics after treatment with plasma in polymeric materials, such as the aging phenomenon, calls the attention of research in the area of nonthermal plasma technology. In this work, a direct treatment with dielectric-barrier discharge plasma was used on the surfaces of ultrafiltration membranes. The measurements of the contact angle with water, attenuated total reflectance accessory, zeta potential, atomic force microscopy and scanning electron microscopy-MEV were performed on the surfaces to verify changes after plasma treatment and to understand the occurrence and timing of the plasma aging effect. In the analysis of the membrane performance, hydraulic permeation and protein retention tests were performed. The results showed an improvement in wettability and hydrophilic properties in the post-treated membranes. The study of reversibility/aging of the post-plasma surface is important for research that deals with the modification of polymeric membranes. Changes in surface morphology, topography and wettability of the membranes were observed up to seven days after treatment, with a tendency to return to the initial characteristics of the membranes.     

Food-water security and virtual water trade in the Middle East and North Africa

The purpose of this study is to analyze the political economy of food-water security in the water-scarce Middle East and North Africa region. The study deploys the lens of virtual water trade to determine how the region's economies have met their rising food-water requirements over the past three decades. It is shown that the region's water and food security currently depend to a considerable extent on water from outside the region, ‘embedded’ in food imports and accessed through trade. The analysis includes blue (surface and groundwater) and green water resources.