Circulating extracellular vesicle-carried PTP1B and PP2A phosphatases as regulators of insulin resistance.

Aims/hypothesis: Metabolic disorders associated with abdominal obesity, dyslipidaemia, arterial hypertension and hyperglycaemia are risk factors for the development of insulin resistance. Extracellular vesicles (EVs) may play an important role in the regulation of metabolic signalling pathways in insulin resistance and associated complications.

Methods: Circulating large EVs (lEVs) and small EVs (sEVs) from individuals with (IR group) and without insulin resistance (n-IR group) were isolated and characterised.

Mesenchymal stem cell-derived extracellular vesicles exert pro-angiogenic and pro-lymphangiogenic effects in ischemic tissues by transferring various microRNAs and proteins including ITGa5 and NRP1.

Mesenchymal stem cells/stromal cells (MSCs)-derived extracellular vesicles (EVs) mediate pro-regenerative effects in damaged ischemic tissues by regulating angiogenesis. MSCs-EVs modulate functions of cells including endogenous mature cells, progenitors and stem cells, resulting in restoration of blood flow. However, the mechanisms underlying such MSC-EV activity still remain poorly understood.

Extracellular vesicles are carriers of adiponectin with insulin-sensitizing and anti-inflammatory properties.

Recent evidence supporting that adipose tissue (AT)-derived extracellular vesicles (EVs) carry an important part of the AT secretome led us to characterize the EV-adipokine profile. In addition to evidencing a high AT-derived EV secretion ability that is further increased by obesity, we identify enrichment of oligomeric forms of adiponectin in small EVs (sEVs). This adipokine is mainly distributed at the EV external surface as a result of nonspecific adsorption of soluble adiponectin.

Effects of Large Extracellular Vesicles from Kidney Cancer Patients on the Growth and Environment of Renal Cell Carcinoma Xenografts in a Mouse Model.

Plasma membrane-derived vesicles, also referred to as large extracellular vesicles (lEVs), are implicated in several pathophysiological situations, including cancer. However, to date, no studies have evaluated the effects of lEVs isolated from patients with renal cancer on the development of their tumors. In this study, we investigated the effects of three types of lEVs on the growth and peritumoral environment of xenograft clear cell renal cell carcinoma in a mouse model.

Linear, weakly nonlinear and fully nonlinear models for soft tissues: which ones provide the most reliable estimations of the stiffness?

Benign and malignant lesions in tissues or organs can be detected by elastographic investigations in which pathological regions are spotted from local alterations of the stiffness. As is known, the shear modulus provides a measure of the stiffness of an elastic material. Based on the classical theory of linear elasticity, an elastogram yields estimations of the shear modulus from measurements of the speed of small-amplitude transverse waves propagating in the medium tested.

Nematic shells: new insights in topology- and curvature-induced effects.

Within the framework of continuum theory, we draw a parallel between ferromagnetic materials and nematic liquid crystals confined on curved surfaces, which are both characterized by local interaction and anchoring potentials. We show that the extrinsic curvature of the shell combined with the out-of-plane component of the director field gives rise to chirality effects. This interplay produces an effective energy term reminiscent of the chiral term in cholesteric liquid crystals, with the curvature tensor acting as a sort of anisotropic helicity.

Cooling a spherical nematic shell.

Within the framework of Landau-de Gennes theory for nematic liquid crystals, we study the temperature-induced isotropic-nematic phase transition on a spherical shell under the assumption of degenerate tangential anchoring. Below a critical temperature, a thin layer of nematic coating a microscopic spherical particle exhibits nonuniform textures due to the geometrical frustration. We find the exact value of the critical threshold for the temperature and determine exactly the nematic textures at the transition by means of a weakly nonlinear analysis.

LPS-enriched small extracellular vesicles from metabolic syndrome patients trigger endothelial dysfunction by activation of TLR4.

Background: Metabolic syndrome (MetS) is characterized by a cluster of interconnected risk factors -hyperglycemia, dyslipidemia, hypertension and obesity- leading to an increased risk of cardiovascular events. Small extracellular vesicles (sEVs) can be considered as new biomarkers of different pathologies, and they are involved in intercellular communication. Here, we hypothesize that sEVs are implicated in MetS-associated endothelial dysfunction.

Large Extracellular Vesicle-Associated Rap1 Accumulates in Atherosclerotic Plaques, Correlates With Vascular Risks and Is Involved in Atherosclerosis.

Rationale: Metabolic syndrome (MetS) is a cluster of interrelated risk factors for cardiovascular diseases and atherosclerosis. Circulating levels of large extracellular vesicles (lEVs), submicrometer-sized vesicles released from plasma membrane, from MetS patients were shown to induce endothelial dysfunction, but their role in early stage of atherosclerosis and on vascular smooth muscle cells (SMC) remain to be fully elucidated.

Objective: To determine the mechanisms by which lEVs lead to the progression of atherosclerosis in the setting of MetS.

Linearly polarized waves of finite amplitude in pre-strained elastic materials.

We study the propagation of linearly polarized transverse waves in a pre-strained incompressible isotropic elastic solid. Both finite and small-but-finite amplitude waves are examined. Irrespective of the magnitude of the wave amplitude, these waves may propagate only if the (unit) normal to the plane spanned by the directions of propagation and polarization is a principal direction of the left Cauchy-Green deformation tensor associated with the pre-strained state.

Phostine 3.1a as a pharmacological compound with antiangiogenic properties against diseases with excess vascularization.

Angiogenesis is a complex process leading to the growth of new blood vessels from existing vasculature, triggered by local proangiogenic factors such as VEGF. An excess of angiogenesis is a recurrent feature of various pathologic conditions such as tumor growth. Phostines are a family of synthetic glycomimetic compounds that exhibit anticancer properties, and the lead compound 3-hydroxy-4,5-bis-benzyloxy-6-benzyloxymethyl-2-phenyl2-oxo-2λ5-[1,2]oxaphosphinane (PST 3.

Phenotyping of circulating extracellular vesicles (EVs) in obesity identifies large EVs as functional conveyors of Macrophage Migration Inhibitory Factor.

Objective: Obesity-associated metabolic dysfunctions are linked to dysregulated production of adipokines. Accumulating evidence suggests a role for fat-derived extracellular vesicles (EVs) in obesity-metabolic disturbances. Since EVs convey numerous proteins we aimed to evaluate their contribution in adipokine secretion.

Microparticles harbouring Sonic hedgehog morphogen improve the vasculogenesis capacity of endothelial progenitor cells derived from myocardial infarction patients.

Aims: Endothelial progenitor cells (EPC) play a role in endothelium integrity maintenance and regeneration. Decreased numbers of EPC or their impaired function correlates with an increase in cardiovascular events. Thus, EPC are important predictors of cardiovascular mortality and morbidity.

Glycosylation as new pharmacological strategies for diseases associated with excessive angiogenesis.

Angiogenesis is a complex process describing the growth of new blood vessels from existing vasculature, and is triggered by local pro-angiogenic factors, such as vascular endothelial growth factor (VEGF), which increase the metabolism of endothelial cells (ECs). Angiogenesis takes part in various physiological conditions such as embryogenesis, placental growth, and in pathological conditions such as tumor growth, diabetic retinopathy, rheumatoid arthritis (RA) and ischemic diseases. Current therapies against excessive angiogenesis target vascular growth signaling.

Influence of the extrinsic curvature on two-dimensional nematic films.

Nematic films are thin fluid structures, ideally two dimensional, endowed with an in-plane degenerate nematic order. In this paper we examine a generalization of the classical Plateau problem to an axisymmetric nematic film bounded by two coaxial parallel rings. At equilibrium, the shape of the nematic film results from the competition between surface tension, which favors the minimization of the area, and the nematic elasticity, which instead promotes the alignment of the molecules along a common direction.

Extract Enriched in Flavan-3-ols and Mainly Procyanidin Dimers Improves Metabolic Alterations in a Mouse Model of Obesity-Related Disorders Partially via Estrogen Receptor Alpha.

Red wine polyphenol extracts improve cardiovascular and metabolic disorders linked to obesity. Their vascular protection is mediated by the activation of the alpha isoform of the estrogen receptor (ERα). In the present study, we explored the effects of a grape seed extract (GSE) enriched in the flavan-3-ols procyanidin dimers on obesity-related cardiovascular and metabolic disorders; with a particular interest in the role/contribution of ERα.

Wrinkles and creases in the bending, unbending and eversion of soft sectors.

We study what is clearly one of the most common modes of deformation found in nature, science and engineering, namely the large elastic bending of curved structures, as well as its inverse, unbending, which can be brought beyond complete straightening to turn into eversion. We find that the suggested mathematical solution to these problems always exists and is unique when the solid is modelled as a homogeneous, isotropic, incompressible hyperelastic material with a strain-energy satisfying the strong ellipticity condition. We also provide explicit asymptotic solutions for thin sectors.

Microparticles Carrying Peroxisome Proliferator-Activated Receptor Alpha Restore the Reduced Differentiation and Functionality of Bone Marrow-Derived Cells Induced by High-Fat Diet.

Metabolic pathologies such as diabetes and obesity are associated with decreased level of circulating and bone marrow (BM)-derived endothelial progenitor cells (EPCs). It is known that activation of peroxisome proliferator-activated receptor alpha (PPARα) may stimulate cell differentiation. In addition, microparticles (MPs), small membrane vesicles produced by activated and apoptotic cells, are able to reprogram EPCs.

Estrogen Receptor α Participates to the Beneficial Effect of Red Wine Polyphenols in a Mouse Model of Obesity-Related Disorders.

Red wine polyphenol extracts (polyphenols) ameliorate cardiovascular and metabolic disorders associated with obesity. Previously, we demonstrated that the alpha isoform of estrogen receptor (ERα) triggers the vascular protection of polyphenols. Here, we investigated the contribution of ERα on the effects of polyphenols on cardiovascular and metabolic alterations associated with obesity.

Activation of Endothelial Pro-resolving Anti-Inflammatory Pathways by Circulating Microvesicles from Non-muscular Myosin Light Chain Kinase-Deficient Mice.

Microvesicles, small membrane vesicles released from cells, have beneficial and/or deleterious effects in sepsis. We previously reported that non-muscle myosin light chain kinase (nmMLCK) deletion protects mice against endotoxic shock by reducing inflammation. Here, we have evaluated the consequences of nmMLCK deletion on microvesicle phenotypes and their effects on mouse aortic endothelial cells in association with vascular inflammation and endothelial dysfunction during endotoxic shock induced by lipopolysaccharide in mice.

Hydrodynamic theory for nematic shells: The interplay among curvature, flow, and alignment.

We derive the hydrodynamic equations for nematic liquid crystals lying on curved substrates. We invoke the Lagrange-Rayleigh variational principle to adapt the Ericksen-Leslie theory to two-dimensional nematics in which a degenerate anchoring of the molecules on the substrate is enforced. The only constitutive assumptions in this scheme concern the free-energy density, given by the two-dimensional Frank potential, and the density of dissipation which is required to satisfy appropriate invariance requirements.

Low concentration of ethanol favors progenitor cell differentiation and neovascularization in high-fat diet-fed mice model.

Endothelial progenitor cells (EPCs) and monocytic cells from bone marrow (BM) can be recruited to the injured endothelium and contribute to its regeneration. During metabolic diseases such as obesity and diabetes, progenitor cell function is impaired. Several studies have shown that moderate alcohol consumption prevents the development and progression of atherosclerosis in a variety of animal/mouse models and increases mobilization of progenitor cells.

Temporal Cross Talk Between Endoplasmic Reticulum and Mitochondria Regulates Oxidative Stress and Mediates Microparticle-Induced Endothelial Dysfunction.

Aims: Circulating microparticles (MPs) from metabolic syndrome patients and those generated from apoptotic T cells induce endothelial dysfunction; however, the molecular and cellular mechanism(s) underlying in the effects of MPs remain to be elucidated.

Results: Here, we show that both types of MPs increased expression of endoplasmic reticulum (ER) stress markers, X-box binding protein 1, p-eukaryotic translation initiation factor 2 α, and CHOP, and nuclear translocation of activating transcription factor 6 on human aortic endothelial cells (HAoECs). MPs decreased in vitro nitric oxide release by HAoECs, whereas in vivo MP injection into mice impaired the endothelium-dependent relaxation induced by acetylcholine.