Maternal body mass index and placental weight: a role for fetal insulin, maternal insulin and leptin.

Purpose: Placental weight (PW) has been found to mediate the main effect of maternal BMI on fetal size. Still, the BMI-PW association is poorly understood. Therefore, we aimed to explore potential explanatory variables, including gestational weight gain (GWG), early- and late-pregnancy circulating levels of maternal glucose, insulin, leptin, adiponectin, triglycerides, LDL-C, and HDL-C, and fetal insulin.

Serglycin Is Involved in TGF-β Induced Epithelial-Mesenchymal Transition and Is Highly Expressed by Immune Cells in Breast Cancer Tissue.

Serglycin is a proteoglycan highly expressed by immune cells, in which its functions are linked to storage, secretion, transport, and protection of chemokines, proteases, histamine, growth factors, and other bioactive molecules. In recent years, it has been demonstrated that serglycin is also expressed by several other cell types, such as endothelial cells, muscle cells, and multiple types of cancer cells. Here, we show that serglycin expression is upregulated in transforming growth factor beta (TGF-β) induced epithelial-mesenchymal transition (EMT).

PTEN and DNA Ploidy Status by Machine Learning in Prostate Cancer.

Machine learning (ML) is expected to improve biomarker assessment. Using convolution neural networks, we developed a fully-automated method for assessing PTEN protein status in immunohistochemically-stained slides using a radical prostatectomy (RP) cohort ( = 253). It was validated according to a predefined protocol in an independent RP cohort ( = 259), alone and by measuring its prognostic value in combination with DNA ploidy status determined by ML-based image cytometry.

Antirheumatic treatment is associated with reduced serum Syndecan-1 in Rheumatoid Arthritis.

The endothelial glycocalyx (EG) is essential for proper function of the endothelium and for vascular integrity, but its role in premature atherogenesis in rheumatoid arthritis (RA) has not been studied yet. EG impairment can play a role in pathogenesis of vascular disease, and one of its characteristics is shedding of syndecan-1 from endothelial cells. Syndecan-1 shedding is mediated by matrix metalloproteinase-9 (MMP-9) and counteracted by tissue inhibitor of metalloproteinases (TIMP)-1.

Mediators Linking Maternal Weight to Birthweight and Neonatal Fat Mass in Healthy Pregnancies.

Context: Lifestyle interventions have not efficaciously reduced complications caused by maternal weight on fetal growth, requiring insight into explanatory mediators.

Objective: We hypothesized that maternal mediators, including adiponectin, leptin, insulin, and glucose, mediate effects of pregestational BMI (pBMI) and gestational weight gain (GWG) on birthweight and neonatal fat mass percentage (FM%) through placental weight and fetal mediators, including insulin levels (Ifv) and venous-arterial glucose difference (ΔGfva). Hypothesized confounders were maternal age, gestational age, and parity.

NBEAL1 controls SREBP2 processing and cholesterol metabolism and is a susceptibility locus for coronary artery disease.

Dysregulated cholesterol homeostasis promotes the pathology of atherosclerosis, myocardial infarction and strokes. Cellular cholesterol is mainly regulated at the transcriptional level by SREBP2, but also through uptake of extracellular cholesterol from low density lipoproteins (LDL) via expression of LDL receptors (LDLR) at the cell surface. Identification of the mechanisms involved in regulation of these processes are thus key to understand the pathology of coronary artery disease.

Acute exercise increases syndecan-1 and -4 serum concentrations.

The effects of acute and long-term exercise on syndecans and the relationship to insulin sensitivity are not fully explored. We aimed to examine the effects of acute and 12 weeks of exercise on (1) serum levels of syndecan-1 and -4, (2) gene expression related to syndecan synthesis and modification in skeletal muscle and adipose tissue, and (3) the relationship to insulin sensitivity. Sedentary men with (n = 13) or without (n = 13) dysglycemia underwent two 45 min acute bicycle tests interspersed by 12 weeks of exercise intervention.

Matrix metalloproteinase-9 mediated shedding of syndecan-4 in glomerular endothelial cells.

Background: Diabetic nephropathy is the most common cause of end-stage renal failure in the western world and Asia. The mechanisms are not fully elucidated, but disruption of glomerular endothelial glycocalyx and shedding of its components including syndecans has been implicated.

Aims: We hypothesize that reduced glomerular filtration in diabetes is caused by disruption of endothelial glycocalyx in glomeruli, including increased shedding of syndecan-4.

Mechanical stress alters the expression of calcification-related genes in vascular interstitial and endothelial cells.

Objectives: Vascular wall calcification is a major pathophysiological component of atherosclerotic disease with many similarities to osteogenesis. Mechanical stress of the vascular wall may theoretically contribute to the proliferative processes by endothelial and interstitial cells. The aim of the study was to investigate the effect of mechanical stress on the expression of some calcification-related genes in primary human endothelial and interstitial cells, and how endothelial cells may stimulate the fibroblast and smooth muscle cells.

Gender differences in the association of syndecan-4 with myocardial infarction: The population-based Tromsø Study.

Background And Aims: Cardiovascular disease is a common cause of morbidity and mortality, with gender differences in pathophysiology. The endothelial glycocalyx maintains vascular integrity, and glycocalyx shedding reflects endothelial dysfunction and early atherosclerosis. Syndecan-1 and -4 are components of the glycocalyx, and increased serum levels indicate glycocalyx damage.

Glucosamine exposure reduces proteoglycan synthesis in primary human endothelial cells in vitro.

Purpose: Glucosamine (GlcN) supplements are promoted for medical reasons, for example, for patients with arthritis and other joint-related diseases. Oral intake of GlcN is followed by uptake in the intestine, transport in the circulation and thereafter delivery to chondrocytes. Here, it is postulated to have an effect on synthesis and turnover of extracellular matrix constituents expressed by these cells.

Increased levels of inflammatory mediators and proinflammatory monocytes in patients with type I diabetes mellitus and nephropathy.

Aims: To investigate and describe the relationship between diabetic nephropathy and systemic inflammation in patients with type 1 diabetes mellitus (T1DM).

Methods: Patients with T1DM, with or without reduced renal function due to diabetic nephropathy, were included. Differences in inflammatory mediators, adhesion molecules, markers of endothelial dysfunction and subsets of monocytes were studied in patients with mean disease duration of 31years.

Serglycin in Quiescent and Proliferating Primary Endothelial Cells.

Proteoglycans are fundamental components of the endothelial barrier, but the functions of the proteoglycan serglycin in endothelium are less described. Our aim was to describe the roles of serglycin in processes relevant for endothelial dysfunction. Primary human umbilical vein endothelial cells (HUVEC) were cultured in vitro and the expression of proteoglycans was investigated.

Serglycin is part of the secretory repertoire of LPS-activated monocytes.

Monocytes play multiple roles in the immune system, and are active in both acute and chronic diseases. Patients exposed to bacterial infections depend on monocytes in defense reactions, but excessive immune reactions may also cause morbidity through systemic inflammatory responses. Few studies have addressed the importance of proteoglycans, and in particular, the hematopoietic serglycin, in such monocyte immune reactions.

Syndecan-4 is a major syndecan in primary human endothelial cells in vitro, modulated by inflammatory stimuli and involved in wound healing.

Syndecans are important cell surface proteoglycans with many functions; yet, they have not been studied to a very large extent in primary human endothelial cells. The purpose of this study was to investigate syndecan-4 expression in cultured human umbilical vein endothelial cells (HUVECs) and assess its role in inflammatory reactions and experimental wound healing. qRT-PCR analysis revealed that syndecan-3 and syndecan-4 were highly expressed in HUVECs, whereas the expression of syndecan-1 and -2 was low.

Effects of restoring normoglycemia in type 1 diabetes on inflammatory profile and renal extracellular matrix structure after simultaneous pancreas and kidney transplantation.

Aims: Patients with type 1 diabetes and end-stage renal disease with simultaneous pancreas and kidney (SPK) or kidney transplants alone (KA) were recruited 9-12 years post transplantation. We investigated differences between these groups with regard to inflammatory parameters and long-term structural changes in kidneys.

Methods: Blood samples were analyzed by ELISA and multiplex for chemokines, cytokines, growth factors, cell adhesion molecules and matrix metalloproteinases.

In patients with type 1 diabetes simultaneous pancreas and kidney transplantation preserves long-term kidney graft ultrastructure and function better than transplantation of kidney alone.

Aims/hypothesis: In patients with type 1 diabetes and end-stage renal disease (ESRD) we aimed to determine whether long-term normoglycaemia, as achieved by successful simultaneous pancreas and kidney (SPK) transplantation, would preserve kidney graft structure and function better than live donor kidney (LDK) transplantation alone.

Methods: Estimated GFR (eGFR) was calculated in SPK (n = 25) and LDK (n = 17) recipients in a stable phase 3 months after transplantation and annually during follow-up. Kidney graft biopsies were obtained at follow-up for measurement of glomerular volume (light microscopy), glomerular basement membrane (GBM) and podocyte foot process widths and mesangial volume fraction (electron microscopy).

Serglycin secretion is part of the inflammatory response in activated primary human endothelial cells in vitro.

Background: Endothelial cells have important functions in e.g. regulating blood pressure, coagulation and host defense reactions.

Reduced sulfation of chondroitin sulfate but not heparan sulfate in kidneys of diabetic db/db mice.

Heparan sulfate proteoglycans are hypothesized to contribute to the filtration barrier in kidney glomeruli and the glycocalyx of endothelial cells. To investigate potential changes in proteoglycans in diabetic kidney, we isolated glycosaminoglycans from kidney cortex from healthy db/+ and diabetic db/db mice. Disaccharide analysis of chondroitin sulfate revealed a significant decrease in the 4-O-sulfated disaccharides (D0a4) from 65% to 40%, whereas 6-O-sulfated disaccharides (D0a6) were reduced from 11% to 6%, with a corresponding increase in unsulfated disaccharides.

Heparan sulfate expression is affected by inflammatory stimuli in primary human endothelial cells.

In diabetes the endothelium is either chronically or transiently exposed to hyperglycemic conditions. In addition, endothelial dysfunction in diabetes is related to changes in the inflammatory response and the turnover of extracellular matrix. This study was undertaken to study the effects of inflammatory stimuli on one particular matrix component, the heparan sulfate (HS) proteoglycans (PGs) synthesized by primary human umbilical cord vein endothelial cells (HUVEC).

Serglycin is a major proteoglycan in polarized human endothelial cells and is implicated in the secretion of the chemokine GROalpha/CXCL1.

Proteoglycan (PG) expression was studied in primary human umbilical vein endothelial cells (HUVEC). RT-PCR analyses showed that the expression of the PG serglycin core protein was much higher than that of the extracellular matrix PG decorin and the cell surface PG syndecan-1. PG biosynthesis was further studied by biosynthetic [(35)S]sulfate labeling of polarized HUVEC.