Upregulation of miR145 and miR126 in EVs from Renal Cells Undergoing EMT and Urine of Diabetic Nephropathy Patients

Simple SummaryDiabetic nephropathy is one of the most frequent complications of diabetes, resulting from diffuse damage to different kidney cells. The identification of subjects at risk is mandatory to prevent its development and provide appropriate therapies reducing the unmanageable evolution towards end-stage kidney disease. The aim of this work was to identify urinary-derived extracellular vesicles (EVs) miRNA cargo to be used as biomarker of kidney damage in diabetic patients. The miRNA profile was then correlated with the molecular mechanism associated with the glomerular and tubular damage using a diabetic-like model. In patients, miR145 and miR126 in urinary EVs increased together with albuminuria. MiR145 and miR126 increased in parallel in EVs from renal epithelial cells undergoing transition to a fibrotic mesenchymal phenotype. These data unveiled a role for miR126 and miR145 as the biomarkers of damage progression and proteinuria development in diabetic nephropathy. AbstractDiabetic nephropathy (DN) is a severe kidney-related complication of type 1 and type 2 diabetes and the most frequent cause of end-stage kidney disease. Extracellular vesicles (EVs) present in the urine mainly derive from the cells of the nephron, thus representing an interesting tool mirroring the kidney’s physiological state. In search of the biomarkers of disease progression, we here assessed a panel of urinary EV miRNAs previously related to DN in type 2 diabetic patients stratified based on proteinuria levels. We found that during DN progression, miR145 and miR126 specifically increased in urinary EVs from diabetic patients together with albuminuria. In vitro, miRNA modulation was assessed in a model of TGF-β1-induced glomerular damage within a three-dimensional perfusion system, as well as in a model of tubular damage induced by albumin and glucose overload. Both renal tubular cells and podocytes undergoing epithelial to mesenchymal transition released EVs containing increased miR145 and miR126 levels. At the same time, miR126 levels were reduced in EVs released by glomerular endothelial cells. This work highlights a modulation of miR126 and miR145 during the progression of kidney damage in diabetes as biomarkers of epithelial to mesenchymal transition.     

A far-near field transformation using the fast multipole techniques

We are interested in deducing the coupling between an antenna and some surrounding structures via the only knowledge of the antenna far-field measured in an anechoic room. A new approach based on a multipole expansion of the Green's kernel is considered to evaluate the field in the vicinity of the antenna. Some numerical experiments illustrate the efficiency of the multipole techniques compared to the physical optic approach.     

Cooperative Modulation of Mineral Growth by Prismatic-Associated Asprich Sequences and Mg(II)

Cooperative effects of magnesium ions and acidic polypeptides originating from a family of proteins known as Asprich (mollusk Atrina rigida) were studied. In our previous studies, these two acidic polypeptides were found to be effective in controlling the morphology of the calcium carbonate mineral, the main inorganic constituent of prismatic layer of the mollusk shell. Since these Asprich sequences are believed to contain a putative magnesium binding domain, the morphology-controlling effects were further investigated with the addition of magnesium ions. The mineral morphology was dramatically changed by the combined influence of each polypeptides and the magnesium ions, substantiating the recognized importance of magnesium in the formation of calcium carbonate-based biominerals.     

An eddy‐current and micromagnetism model with applicationsto disk write heads

As data rates increase and the size of the disk write head decreases it is likely that a standard non‐linear eddy‐current simulation of a disk write head will not fully capture dynamic effects. In this paper we propose a coupled eddy‐current and micromagnetics model for the disk write head. We present a simple finite difference formulation derived from a mass‐lumped finite element method. This derivation allows us to verify that, before time discretization, the semi‐discrete scheme obeys the same energy decay equality as the partial differential equation model. We show some numerical results for an ‘academic’ disk writer model. Copyright © 2004 John Wiley & Sons, Ltd.     

Nutritional metabonomics: an approach to promote personalized health and wellness

Nutritional research has emerged in the last century from the study of nutrients as a means of nourishment to the general population to the quest for wellness improvement through specific food components. Advances in nutrigenomics technologies have allowed nutrition scientists to be for the first time at the forefront of nutritional research. Such advances have given them the ability to discern new vital scientific discoveries specifically for the development of new tailored dietary patterns. In this, nutritional metabonomics has rapidly evolved into a very powerful bioanalytical tool able to assess multi-parametric metabolic responses of living organisms to specific dietary interventions. Nutritional metabonomics therefore provides a systematic approach through the comprehensive analysis of metabolites aiming today at the quest for homeostatic balance which is dependent not only on the host but also on the crucial metabolic interactions with microbial symbionts.     

Differential Therapeutic Effect of Extracellular Vesicles Derived by Bone Marrow and Adipose Mesenchymal Stem Cells on Wound Healing of Diabetic Ulcers and Correlation to Their Cargoes

Extracellular vesicles (EVs) derived from mesenchymal stem cells isolated from both bone marrow (BMSCs) and adipose tissue (ADSCs) show potential therapeutic effects. These vesicles often show a similar beneficial effect on tissue regeneration, but in some contexts, they exert different biological properties. To date, a comparison of their molecular cargo that could explain the different biological effect is not available. Here, we demonstrated that ADSC-EVs, and not BMSC-EVs, promote wound healing on a murine model of diabetic wounds. Besides a general similarity, the bioinformatic analysis of their protein and miRNA cargo highlighted important differences between these two types of EVs. Molecules present exclusively in ADSC-EVs were highly correlated to angiogenesis, whereas those expressed in BMSC-EVs were preferentially involved in cellular proliferation. Finally, in vitro analysis confirmed that both ADSC and BMSC-EVs exploited beneficial effect on cells involved in skin wound healing such as fibroblasts, keratinocytes and endothelial cells, but through different cellular processes. Consistent with the bioinformatic analyses, BMSC-EVs were shown to mainly promote proliferation, whereas ADSC-EVs demonstrated a major effect on angiogenesis. Taken together, these results provide deeper comparative information on the cargo of ADSC-EVs and BMSC-EVs and the impact on regenerative processes essential for diabetic wound healing.     

Nonlinear elastic inversion of prestack marine seismic data

A horizontally stratified medium consisting of a fluid layer overlaying any number of solid layers is considered. The depth distribution of the density and of the two elastic parameters from prestack offshore surface data is to be determined. The inverse problem is posed in terms of optimization. Its solution is based on nonlinear least squares. Since the solution of the direct problem is an important point in the inversion algorithm, a variational formulation capable of solving the (well-known) numerical difficulty at the liquid-solid interface is used. The acoustoelastic aspect of the problem is stressed. The feasibility of the technique is shown for large-size synthetic examples. It is expected that acoustoelastic inversion will help improve the interpretation of offshore seismic data     

Metabotropic Glutamate Receptor Blockade Reduces Preservation Damage in Livers from Donors after Cardiac Death

We previously demonstrated that the blockade of mGluR5 by 2-methyl-6(phenylethynyl)pyridine (MPEP) reduces both cold and warm ischemia/reperfusion injury. Here we evaluated whether MPEP reduces the hepatic preservation injury in rat livers from cardiac-death-donors (DCDs). Livers from DCD rats were isolated after an in situ warm ischemia (30 min) and preserved for 22 h at 4 °C with UW solution. Next, 10 mg/Kg MPEP or vehicle were administered 30 min before the portal clamping and added to the UW solution (3 µM). LDH released during washout was quantified. Liver samples were collected for iNOS, eNOS, NO, TNF-α, ICAM-1, caspase-3 and caspase-9 protein expression and nuclear factor-erythroid-2-related factor-2 (Nrf2) gene analysis. Lower LDH levels were detected in control grafts versus DCD groups. An increase in eNOS and NO content occurred after MPEP treatment; iNOS and TNF-α content was unchanged. ICAM-1 expression was reduced in the MPEP-treated livers as well as the levels of caspase-3 and caspase-9. Nrf2, oxidative stress-sensitive gene, was recovered to control value by MPEP. These results suggest that MPEP can be used to reclaim DCD livers subjected to an additional period of cold ischemia during hypothermic storage. MPEP protects against apoptosis and increased eNOS, whose overexpression has been previously demonstrated to be protective in hepatic ischemia/reperfusion damage.