Morphological and functional adaptations of pancreatic alpha-cells during late pregnancy in the mouse.

Background: Pregnancy represents a major metabolic challenge for the mother, and involves a compensatory response of the pancreatic beta-cell to maintain normoglycemia. However, although pancreatic alpha-cells play a key role in glucose homeostasis and seem to be involved in gestational diabetes, there is no information about their potential adaptations or changes during pregnancy.

Material And Methods: Non-pregnant (controls) and pregnant C57BL/6 mice at gestational day 18.

Gelsolin: a new biomarker of disease activity in SLE patients associated with HDL-c.

Objectives: To identify potential biomarkers of disease activity analysing the proteome of high-density lipoprotein (HDL) particles from SLE patients in clinical remission and when they develop a flare compared with a healthy control group.

Methods: Quantitative proteomic analyses of purified HDL were performed using Tandem Mass Tag isobaric tag-labelling and nanoLC-Orbitrap (nLC-MS/MS) from nine SLE patients in clinical remission when they developed a flare and from nine healthy controls (9-9-9). We verified the identified proteins by Western blot and ELISA in a cohort of 104 SLE women patients, 46 healthy women and 14 SLE patients when a flare developed.

Lipid Profiling Using H NMR Spectroscopy.

Lipid profiling, which includes fatty acids, phospholipids, glycerides, and cholesterols is extremely important because of the essential role lipids play in the regulation of metabolism in animals. H-NMR-based protocols for high-throughput lipid analysis in complex mixtures have been developed and applied to biological systems. Many classes of lipids can be quantitatively analyzed in many sample matrices including serum, cells, and tissues using a simple H NMR experiment.

Podocyte and tubular involvement in AngioJet-induced kidney injury.

The AngioJet technique combines localized thrombolysis and percutaneous mechanical thrombectomy (PMT). However, PMT may cause acute kidney injury (AKI), which has been ascribed to severe mechanical haemolysis, although no renal biopsies have been reported. We now report the first renal biopsy in a patient with AKI following PMT.

rMSIKeyIon: An Ion Filtering R Package for Untargeted Analysis of Metabolomic LDI-MS Images.

Many MALDI-MS imaging experiments make a case versus control studies of different tissue regions in order to highlight significant compounds affected by the variables of study. This is a challenge because the tissue samples to be compared come from different biological entities, and therefore they exhibit high variability. Moreover, the statistical tests available cannot properly compare ion concentrations in two regions of interest (ROIs) within or between images.

HDL Triglycerides: A New Marker of Metabolic and Cardiovascular Risk.

While cholesterol content in high-density lipoproteins (HDLs) is a well-established inverse marker of cardiovascular risk, the importance of HDL-triglyceride (HDL-TG) concentration is not well known. We aim to examine plasma HDL-TG concentrations, assessed by H-NMR, in patients with metabolic diseases and their association with classical biomarkers. In this cross-sectional study, we included 502 patients with type 2 diabetes or metabolic syndrome attending the lipid unit of our University Hospital.

Cost-Effective, Safe, and Personalized Cell Therapy for Critical Limb Ischemia in Type 2 Diabetes Mellitus.

Cell therapy is a progressively growing field that is rapidly moving from preclinical model development to clinical application. Outcomes obtained from clinical trials reveal the therapeutic potential of stem cell-based therapy to deal with unmet medical treatment needs for several disorders with no therapeutic options. Among adult stem cells, mesenchymal stem cells (MSCs) are the leading cell type used in advanced therapies for the treatment of autoimmune, inflammatory and vascular diseases.

Umbilical Cord miRNAs in Small-for-Gestational-Age Children and Association With Catch-Up Growth: A Pilot Study.

Context: Catch-up growth in infants who are small for gestational age (SGA) is a risk factor for the development of cardiometabolic diseases in adulthood. The basis and mechanisms underpinning catch-up growth in newborns who are SGA are unknown.

Objective: To identify umbilical cord miRNAs associated with catch-up growth in infants who are SGA and study their relationship with offspring's cardiometabolic parameters.

Body fat anthropometric indexes: Which of those identify better high cardiovascular risk subjects? A comparative study in Spanish population.

Aim: To determine the association of body mass index (BMI), waist circumference (WC), waist to hip ratio (WHR), waist to height ratio (WHtr) and Body Shape Index (ABSI) with high cardiovascular risk (CVR), as well as to determine whether how strong are these relationships.

Material And Methods: A cross-sectional study was carried out in Spanish Caucasian adults. 3,456 subjects completed the study, 45.

Systemic Inflammation in Metabolic Syndrome: Increased Platelet and Leukocyte Activation, and Key Role of CXCL1/CXCR1 and CCL2/CCR2 Axes in Arterial Platelet-Proinflammatory Monocyte Adhesion.

Background: Metabolic syndrome is associated with low-grade systemic inflammation, which is a key driver of premature atherosclerosis. We characterized immune cell behavior in metabolic syndrome, its consequences, and the potential involvement of the CXCL1/CXCR1 and CCL2/CCR2 chemokine axes.

Methods: Whole blood from 18 patients with metabolic syndrome and 21 age-matched controls was analyzed by flow cytometry to determine the leukocyte immunophenotypes, activation, platelet-leukocyte aggregates, and CXCR1 expression.

Glomerular Hematuria: Cause or Consequence of Renal Inflammation?

Glomerular hematuria is a cardinal symptom of renal disease. Glomerular hematuria may be classified as microhematuria or macrohematuria according to the number of red blood cells in urine. Recent evidence suggests a pathological role of persistent glomerular microhematuria in the progression of renal disease.

Fatty acid binding protein 4 (FABP4) as a potential biomarker reflecting myocardial lipid storage in type 2 diabetes.

Objective: Fatty acid binding protein 4 (FABP4) is an intracellular lipid chaperone involved in the crosstalk between adipose and peripheral tissues, and it contributes to widespread insulin resistance in cells, including cardiac cells. However, the role of this adipokine in regulating cardiac metabolism and myocardial neutral lipid content in patients with type 2 diabetes has not been elucidated.

Methods: The impact of circulating FABP4 on the cardiac neutral lipid content was measured by proton magnetic resonance spectroscopy (H-MRS) in patients with type 2 diabetes.

Interleukin-17A blockade reduces albuminuria and kidney injury in an accelerated model of diabetic nephropathy.

Diabetic nephropathy (DN) is one of the most common complications of diabetes, and currently the first end-stage renal disease worldwide. New strategies to treat DN using agents that target inflammatory pathways have attracted special interest. Recent pieces of evidences suggest a promising effect of IL-17A, the Th17 effector cytokine.

Review of the scientific evolution of gene therapy for the treatment of homozygous familial hypercholesterolaemia: past, present and future perspectives.

Familial hypercholesterolaemia (FH) is a devastating genetic disease that leads to extremely high cholesterol levels and severe cardiovascular disease, mainly caused by mutations in any of the main genes involved in low-density lipoprotein cholesterol (LDL-C) uptake. Among these genes, mutations in the LDL receptor () are responsible for 80%-90% of the FH cases. The severe homozygous variety (HoFH) is not successfully treated with standard cholesterol-lowering therapies, and more aggressive strategies must be considered to mitigate the effects of this disease, such as weekly/biweekly LDL apheresis.

Palmitate decreases migration and proliferation and increases oxidative stress and inflammation in smooth muscle cells: role of the Nrf2 signaling pathway.

Fatty acids are essential to cell functionality and may exert diverging vascular effects including migration, proliferation, oxidative stress, and inflammation. This study examined the effect of palmitate on human coronary artery smooth muscle cell (HCASMC) function. An in vitro wound-healing assay indicated that palmitate decreased HCASMC migration in dose- and time-dependent manners.

Assessing the potential of sputtered gold nanolayers in mass spectrometry imaging for metabolomics applications.

Mass spectrometry imaging (MSI) is a molecular imaging technique that maps the distribution of molecules in biological tissues with high spatial resolution. The most widely used MSI modality is matrix-assisted laser desorption/ionization (MALDI), mainly due to the large variety of analyte classes amenable for MALDI analysis. However, the organic matrices used in classical MALDI may impact the quality of the molecular images due to limited lateral resolution and strong background noise in the low mass range, hindering its use in metabolomics.

Extracellular FABP4 uptake by endothelial cells is dependent on cytokeratin 1 expression.

Aims: The aim of this study is to determine the physical and functional interplay between fatty acid-binding protein 4 (FABP4) and its membrane receptor-like candidate protein, cytokeratin 1 (CK1), and to determine the effect of hindering CK1-mediated FABP4 cellular uptake on non-disturbed or metabolically stressed endothelial cells.

Methods: We monitored the direct interaction between FABP4 and CK1 using surface plasmon resonance, and the effects of blocking exogenous FABP4 (eFABP4) cellular uptake were determined by using specific siRNA to knock down the expression of CK1 in human umbilical vein endothelial cells (HUVECs). The expression and nuclear translocation of transcription factors involved in oxidative stress (NRF2) and inflammation (p65 subunit of NF-ĸB transcription factor) were determined by Western blotting analysis.

Biomarkers of Exposure to Secondhand and Thirdhand Tobacco Smoke: Recent Advances and Future Perspectives.

Smoking is the leading preventable disease worldwide and passive smoking is estimated to be the cause of about 1.0% of worldwide mortality. The determination of tobacco smoke biomarkers in human biological matrices is key to assess the health effects related to the exposure to environmental tobacco smoke.

mTORC1 Overactivation as a Key Aging Factor in the Progression to Type 2 Diabetes Mellitus.

Type 2 Diabetes Mellitus (T2DM), a worldwide epidemics, is a progressive disease initially developing an insulin resistant state, with manifest pancreatic beta islet overwork and hyperinsulinemia. As the disease progresses, pancreatic β cells are overwhelmed and fails in their capacity to compensate insulin resistance. In addition, it is usually associated with other metabolic diseases such as hyperlipidemia, obesity and the metabolic syndrome.

Gremlin Regulates Tubular Epithelial to Mesenchymal Transition via VEGFR2: Potential Role in Renal Fibrosis.

Chronic kidney disease (CKD) is emerging as an important health problem due to the increase number of CKD patients and the absence of an effective curative treatment. Gremlin has been proposed as a novel therapeutic target for renal inflammatory diseases, acting via Vascular Endothelial Growth Factor Receptor-2 (VEGFR2). Although many evidences suggest that Gremlin could regulate renal fibrosis, the receptor involved has not been yet clarified.

Targeting inflammation in diabetic nephropathy: a tale of hope.

Introduction: Diabetic nephropathy (DN) is the leading cause of chronic kidney disease (CKD) and end-stage renal disease (ESRD). Beyond the new anti-diabetic drugs that possess markedly cardiovascular and renal protective effects, no novel direct therapies for DN have become available on the market in the last twenty years. Recently well-designed clinical trials for the treatment of DN, with attractive pathogenetic rationale, e.

Detecting familial hypercholesterolemia earlier in life by actively searching for affected children:The DECOPIN project.

Background And Aims: Familial hypercholesterolemia (FH) is underdiagnosed in children. We assessed a combination of two screening methods. The first method was to detect hypercholesteraemic children and then study the parents (Ch-P pathway), and the second one was to study the offspring of FH-affected parents (P-Ch pathway).

Pas Kinase Deficiency Triggers Antioxidant Mechanisms in the Liver.

Metabolic dysfunction in the liver is the cause of numerous pathologies, which are associated with an altered redox state. PASK (PAS Domain Kinase) is a nutrient and bioenergetic sensor. We contend that PASK could act as an oxidative stress sensor in liver and/or control the metabolic balance, playing a role in the mitochondrial homeostasis.

Metabolic profiling and targeted lipidomics reveals a disturbed lipid profile in mothers and fetuses with intrauterine growth restriction.

Fetal growth may be impaired by poor placental function or maternal conditions, each of which can influence the transfer of nutrients and oxygen from the mother to the developing fetus. Large-scale studies of metabolites (metabolomics) are key to understand cellular metabolism and pathophysiology of human conditions. Herein, maternal and cord blood plasma samples were used for NMR-based metabolic fingerprinting and profiling, including analysis of the enrichment of circulating lipid classes and subclasses, as well as the number of sub-fraction particles and their size.