Cardiosphere-derived cells suppress allogeneic lymphocytes by production of PGE2 acting via the EP4 receptor

derived cells (CDCs) are a cardiac progenitor cell population, which have been shown to possess cardiac regenerative properties and can improve heart function in a variety of cardiac diseases. Studies in large animal models have predominantly focussed on using autologous cells for safety, however allogeneic cell banks would allow for a practical, cost-effective and efficient use in a clinical setting. The aim of this work was to determine the immunomodulatory status of these cells using CDCs and lymphocytes from 5 dogs. CDCs expressed MHC I but not MHC II molecules and in mixed lymphocyte reactions demonstrated a lack of lymphocyte proliferation in response to MHC-mismatched CDCs. Furthermore, MHC-mismatched CDCs suppressed lymphocyte proliferation and activation in response to Concanavalin A. Transwell experiments demonstrated that this was predominantly due to direct cell-cell contact in addition to soluble mediators whereby CDCs produced high levels of PGE2 under inflammatory conditions. This led to down-regulation of CD25 expression on lymphocytes via the EP4 receptor. Blocking prostaglandin synthesis restored both, proliferation and activation (measured via CD25 expression) of stimulated lymphocytes. We demonstrated for the first time in a large animal model that CDCs inhibit proliferation in allo-reactive lymphocytes and have potent immunosuppressive activity mediated via PGE2

Increased Renal Methylglyoxal Formation with Down-Regulation of PGC-1α-FBPase Pathway in Cystathionine γ-Lyase Knockout Mice

We have previously reported that hydrogen sulfide (H2S), a gasotransmitter and vasodilator has cytoprotective properties against methylglyoxal (MG), a reactive glucose metabolite associated with diabetes and hypertension. Recently, H2S was shown to up-regulate peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α, a key gluconeogenic regulator that enhances the gene expression of the rate-limiting gluconeogenic enzyme, fructose-1,6-bisphosphatase (FBPase). Thus, we sought to determine whether MG levels and gluconeogenic enzymes are altered in kidneys of 6–22 week-old cystathionine γ-lyase knockout (CSE-/-; H2S-producing enzyme) male mice. MG levels were determined by HPLC. Plasma glucose levels were measured by an assay kit. Q-PCR was used to measure mRNA levels of PGC-1α and FBPase-1 and -2. Coupled-enzymatic assays were used to determine FBPase activity, or triosephosphate levels. Experimental controls were either age-matched wild type mice or untreated rat A-10 cells. Interestingly, we observed a significant decrease in plasma glucose levels along with a significant increase in plasma MG levels in all three age groups (6–8, 14–16, and 20–22 week-old) of the CSE-/- mice. Indeed, renal MG and triosephosphates were increased, whereas renal FBPase activity, along with its mRNA levels, were decreased in the CSE-/- mice. The decreased FBPase activity was accompanied by lower levels of its product, fructose-6-phosphate, and higher levels of its substrate, fructose-1,6-bisphosphate in renal extracts from the CSE-/- mice. In agreement, PGC-1α mRNA levels were also significantly down-regulated in 6-22 week-old CSE-/- mice. Furthermore, FBPase-1 and -2 mRNA levels were reduced in aorta tissues from CSE-/- mice. Administration of NaHS, a H2S donor, increased the gene expression of PGC-1α and FBPase-1 and -2 in cultured rat A-10 cells. In conclusion, overproduction of MG in CSE-/- mice is due to a H2S-mediated down-regulation of the PGC-1α-FBPase pathway, further suggesting the important role of H2S in the regulation of glucose metabolism and MG generation

Poly(ethylmethacrylate-co-diethylaminoethyl acrylate) coating improves endothelial re-population, bio-mechanical and anti-thrombogenic properties of decellularized carotid arteries for blood vessel replacement

Decellularized vascular scaffolds are promising materials for vessel replacements. However, despite the natural origin of decellularized vessels, issues such as biomechanical incompatibility, immunogenicity risks and the hazards of thrombus formation, still need to be addressed. In this study, we coated decellularized vessels obtained from porcine carotid arteries with poly (ethylmethacrylate-co-diethylaminoethylacrylate) (8g7) with the purpose of improving endothelial coverage and minimizing platelet attachment while enhancing the mechanical properties of the decellularized vascular scaffolds. The polymer facilitated binding of endothelial cells (ECs) with high affinity and also induced endothelial cell capillary tube formation. In addition, platelets showed reduced adhesion on the polymer under flow conditions. Moreover, the coating of the decellularized arteries improved biomechanical properties by increasing its tensile strength and load. In addition, after 5 days in culture, ECs seeded on the luminal surface of 8g7-coated decellularized arteries showed good regeneration of the endothelium. Overall, this study shows that polymer coating of decellularized vessels provides a new strategy to improve re-endothelialization of vascular grafts, maintaining or enhancing mechanical properties while reducing the risk of thrombogenesis. These results could have potential applications in improving tissue-engineered vascular grafts for cardiovascular therapies with small caliber vessels

Sea Urchins Predation Facilitates Coral Invasion in a Marine Reserve

Macroalgae is the dominant trophic group on Mediterranean infralittoral rocky bottoms, whereas zooxanthellate corals are extremely rare. However, in recent years, the invasive coral Oculina patagonica appears to be increasing its abundance through unknown means. Here we examine the pattern of variation of this species at a marine reserve between 2002 and 2010 and contribute to the understanding of the mechanisms that allow its current increase. Because indirect interactions between species can play a relevant role in the establishment of species, a parallel assessment of the sea urchin Paracentrotus lividus, the main herbivorous invertebrate in this habitat and thus a key species, was conducted. O. patagonica has shown a 3-fold increase in abundance over the last 8 years and has become the most abundant invertebrate in the shallow waters of the marine reserve, matching some dominant erect macroalgae in abundance. High recruitment played an important role in this increasing coral abundance. The results from this study provide compelling evidence that the increase in sea urchin abundance may be one of the main drivers of the observed increase in coral abundance. Sea urchins overgraze macroalgae and create barren patches in the space-limited macroalgal community that subsequently facilitate coral recruitment. This study indicates that trophic interactions contributed to the success of an invasive coral in the Mediterranean because sea urchins grazing activity indirectly facilitated expansion of the coral. Current coral abundance at the marine reserve has ended the monopolization of algae in rocky infralittoral assemblages, an event that could greatly modify both the underwater seascape and the sources of primary production in the ecosystem

Indicators of oral health in older adults with and without the presence of multimorbidity: a cross-sectional study

Horacio Islas-Granillo,1 Socorro Aida Borges-Yañez,2 José de Jesús Navarrete-Hernández,1 Miriam Alejandra Veras-Hernández,1 Juan Fernando Casanova-Rosado,3 Mirna Minaya-Sánchez,3 Alejandro José Casanova-Rosado,3 Miguel Ángel Fernández-Barrera,1 Carlo Eduardo Medina-Solís1,4 1Academic Area of Dentistry, Health Sciences Institute, Autonomous University of Hidalgo State, Pachuca, Mexico; 2DEPeI Faculty of Dentistry, National Autonomous University of Mexico, Ciudad de Mexico, Mexico; 3Faculty of Dentistry, Autonomous University of Campeche, Campeche, Mexico; 4Advanced Studies and Research Center in Dentistry “Dr Keisaburo Miyata”, Faculty of Dentistry, Autonomous University State of Mexico, Toluca, Mexico Purpose: The aim of this study was to determine whether there are differences in the distribution of various indicators of oral health among elderly people with and without multimorbidity (ie, two or more chronic diseases). Subjects and methods: A cross-sectional, comparative study was conducted using a sample of Mexican elderly individuals aged ≥60 years. The average age of the cohort was 79.06±9.78 years, and 69.1% were women. The variables indicating oral health were as follows: functional dentition, edentulism, hyposalivation, xerostomia, root caries and periodontitis. The multimorbidity variable was operationally categorized as follows: 0= subjects with no chronic disease or one chronic disease and 1= subjects with two or more chronic diseases. Questionnaires were used to collect information on various variables regarding general health. Likewise, the participants underwent a clinical oral examination. The analysis was performed using Stata 11.0. Results: The overall prevalence of multimorbidity was 27.3%. The prevalences of various oral health indicators were as follows: without functional dentition 89.9%; hyposalivation 59.7%; edentulism 38.9% and self-reported xerostomia 25.2%. Dental caries were observed in 95.3% of the subjects, and the prevalence of severe periodontitis was 80%. We found a significant difference only in edentulism; its prevalence was higher among subjects with multimorbidity (55.3% vs 32.7%, P=0.015) than among those without multimorbidity. Conclusion: The presence of edentulism in this sample of Mexican older adults was higher in subjects with multimorbidity. Multimorbidity and oral diseases constitute a true challenge in elderly people, because they affect quality of life and are associated with high health care costs. Keywords: older adults, multimorbidity, oral health, edentulism, tooth los

The Peru-Chile Margin from Global Gravity Field Derivatives

Deformation along the 3,500 km subduction Pacific margin of the Peru-Chile trench is partially controlled by ocean bathymetric heterogeneities and sediments. Oceanic highs (e.g. ridges, fracture zones, plateaus) influence deformation in the fore-arc zone where collision occurs, and control turbiditic flow dispersal and consequently the amount of sediments accreted at the frontal accretionary prism and subduction channel, compartmentalizing the trench into segments linked to seismic segmentation. Recent satellite missions (CHAMP, GRACE and GOCE) have introduced an extraordinary improvement in the reconstruction of the global gravity field. Earth gravity field models, mainly derived from satellite measurements, reflect mass inhomogeneities of the earth. This chapter focuses on the determination of mass heterogeneities over the oceanic plate and their relation to general distribution of sediments over the Peru-Chilean margin, seismic segmentation along the margin, and the relationship between trench sediment thickness and the variable Andean orogenic volume, by means of a gravimetric analysis. Using the gravity potential model EGM2008 and satellite GOCE data we calculated two functionals of the geopotential: the Bouguer anomaly and the vertical gravity gradient, both corrected for the topographic effect. The vertical gravity gradient field is of special interest as it highlights main geological features, and allows unraveling unknown structures that are concealed by sediments. From these, different features can be clearly depicted such as the contact between the Pacific oceanic crust and the South American plate, the Nazca Ridge, the Juan Fernandez Ridge and the Chile Rise, among others. The segmentation between a filled trench south of Juan Fernandez Ridge, a partially filled trench to the north up to the Copiapo Ridge, and a completely starved trench north of this latitude is depicted. Finally, the relationship between gravity derived fields, high oceanic features and seismic segmentation is discussed for the last megathrust earthquakes that affected this subductive plate boundary