LMO3 reprograms visceral adipocyte metabolism during obesity.

Obesity and body fat distribution are important risk factors for the development of type 2 diabetes and metabolic syndrome. Evidence has accumulated that this risk is related to intrinsic differences in behavior of adipocytes in different fat depots. We recently identified LIM domain only 3 (LMO3) in human mature visceral adipocytes; however, its function in these cells is currently unknown.

Fractional heat shock protein 27 urine excretion as a short-term predictor in acute exacerbation of chronic obstructive pulmonary disease.

Background: Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality and is characterized by episodes of acute exacerbations. Finding a systemic biomarker that reliably predicts outcome after an acute exacerbation remains a major challenge. Heat shock protein 27 (HSP27) has been previously studied in COPD, however, urine excretion trajectory and prognostic value after an exacerbation is unknown.

PNPLA3 I148M Up-Regulates Hedgehog and Yap Signaling in Human Hepatic Stellate Cells.

Liver fibrosis represents the wound healing response to sustained hepatic injury with activation of hepatic stellate cells (HSCs). The I148M variant of the gene represents a risk factor for development of severe liver fibrosis. Activated HSCs carrying the I148M variant display exacerbated pro-inflammatory and pro-fibrogenic features.

Effects of the ketogenic diet on platelet counts and global coagulation tests in childhood epilepsy.

Purpose: Several antiseizure drugs (ASD), especially Valproic acid (VPA), influence platelet counts and coagulation parameters. The ketogenic diet (KD), established in drug-resistant epilepsy, is combined with ASDs. Bruising and prolonged bleeding times during KD have been described, but whether hemostatic changes result from the KD or from concomitant ASDs, remains unclear.

Heme oxygenase-1 deficiency triggers exhaustion of hematopoietic stem cells.

While intrinsic changes in aging hematopoietic stem cells (HSCs) are well characterized, it remains unclear how extrinsic factors affect HSC aging. Here, we demonstrate that cells in the niche-endothelial cells (ECs) and CXCL12-abundant reticular cells (CARs)-highly express the heme-degrading enzyme, heme oxygenase 1 (HO-1), but then decrease its expression with age. HO-1-deficient animals (HO-1 ) have altered numbers of ECs and CARs that produce less hematopoietic factors.

Prognostic and diagnostic impact of fibrinogen, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio on thymic epithelial tumors outcome.

Background: Peripheral blood-derived inflammation-based markers, such as Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR), and Fibrinogen have been identified as prognostic markers in various solid malignancies. Here we aimed to investigate the prognostic and diagnostic impact of NLR, PLR, and Fibrinogen in patients with thymic epithelial tumors (TETs).

Results: Pretreatment Fibrinogen serum concentrations, NLRs and PLRs were highest in patients with TCs and advanced tumor stages.

Dynamic reference intervals for coagulation parameters from infancy to adolescence.

Introduction: Practical and ethical challenges as well as time and costs have restricted the generation of pediatric reference intervals. Therefore, pediatric reference intervals on coagulation parameters based on solid evidence are still scarce. Furthermore, reference intervals by age-group cannot reflect the dynamics of age and sex specific coagulation values during childhood.

Study of In Vivo Glucose Metabolism in High-fat Diet-fed Mice Using Oral Glucose Tolerance Test (OGTT) and Insulin Tolerance Test (ITT).

Obesity represents the most important single risk factor in the pathogenesis of type 2 diabetes, a disease which is characterized by a resistance to insulin-stimulated glucose uptake and a gross decompensation of systemic glucose metabolism. Despite considerable progress in the understanding of glucose metabolism, the molecular mechanisms of its regulation in health and disease remain under-investigated, while novel approaches to prevent and treat diabetes are urgently needed. Diet derived glucose stimulates the pancreatic secretion of insulin, which serves as the principal regulator of cellular anabolic processes during the fed-state and thus balances blood glucose levels to maintain systemic energy status.

Analytical evaluation of a fully automated immunoassay for faecal calprotectin in a paediatric setting.

Introduction: Faecal calprotectin (FC) is a routinely used marker for identifying and monitoring children with inflammatory bowel disease (IBD). This non-invasive test is useful for screening children with gastrointestinal symptoms to avoid unnecessary invasive procedures. In this study, we validated for the first time the performance of a fully automated particle-enhanced turbidimetric immunoassay (PETIA) on the VITROS® 5600 analyzer for measurement of FC in symptomatic children and adolescents.

MicroRNA-146a governs fibroblast activation and joint pathology in arthritis.

Synovial fibroblasts are key cells orchestrating the inflammatory response in arthritis. Here we demonstrate that loss of miR-146a, a key epigenetic regulator of the innate immune response, leads to increased joint destruction in a TNF-driven model of arthritis by specifically regulating the behavior of synovial fibroblasts. Absence of miR-146a in synovial fibroblasts display a highly deregulated gene expression pattern and enhanced proliferation in vitro and in vivo.

Elevated CRP levels predict poor outcome and tumor recurrence in patients with thymic epithelial tumors: A pro- and retrospective analysis.

Objective: Scarce information exists on the pathogenesis of thymic epithelial tumors (TETs), comprising thymomas, thymic carcinomas (TCs) and neuroendocrine tumors. C-reactive protein (CRP) increases during certain malignancies. We aimed to investigate the clinical relevance of CRP in patients with TETs.

Increased trefoil factor 2 levels in patients with chronic kidney disease.

In chronically damaged tissue, trefoil factor family (TFF) peptides ensure epithelial protection and restitution. In chronic kidney disease (CKD), TFF1 and TFF2 are reported to be upregulated. Especially in the early phase, CKD is associated with silently ongoing renal damage and inflammation.

Chronic Intranasal Insulin Does Not Affect Hepatic Lipids but Lowers Circulating BCAAs in Healthy Male Subjects.

Context: Nonalcoholic fatty liver disease and elevated circulating branched-chain amino acids (BCAAs) are common characteristics of obesity and type 2 diabetes. In rodents, brain insulin signaling controls both hepatic triglyceride secretion and BCAA catabolism. Whether brain insulin signaling controls similar metabolic pathways in humans is unknown.

Hepatic Cholesterol-25-Hydroxylase Overexpression Improves Systemic Insulin Sensitivity in Mice.

Obesity is a major risk factor for several diseases including diabetes, heart disease, and some forms of cancer and due to its rapidly increasing prevalence it has become one of the biggest problems medicine is facing today. All the more surprising, a substantial percentage of obese patients are metabolically healthy when classified based on insulin resistance and systemic inflammation. Oxysterols are naturally occurring molecules that play important role in various metabolic and inflammatory processes and their levels are elevated in patients suffering from obesity and diabetes.

HO-1 inhibits preadipocyte proliferation and differentiation at the onset of obesity via ROS dependent activation of Akt2.

Excessive accumulation of white adipose tissue (WAT) is a hallmark of obesity. The expansion of WAT in obesity involves proliferation and differentiation of adipose precursors, however, the underlying molecular mechanisms remain unclear. Here, we used an unbiased transcriptomics approach to identify the earliest molecular underpinnings occuring in adipose precursors following a brief HFD in mice.

Mast cells are not associated with systemic insulin resistance.

Background: Infiltration of white adipose tissue (WAT) by inflammatory cells in obesity is considered to be a key event in the development of insulin resistance. Recently, mast cells (MCs) have been identified as new players in the pathogenesis of obesity. We aimed to investigate the relationship between MCs and various inflammatory markers in serum and WAT and to determine the role of MCs in the aetiology of insulin resistance.

Heme oxygenase 1 controls early innate immune response of macrophages to Salmonella Typhimurium infection.

Macrophages are central for the immune control of intracellular microbes. Heme oxygenase 1 (HO-1, hmox) is the first and rate limiting enzyme in the breakdown of heme originating from degraded senescent erythrocytes and heme-proteins, yielding equal amounts of iron, carbon monoxide and biliverdin. HO-1 is strongly up-regulated in macrophages in response to inflammatory signals, including bacterial endotoxin.

Plasma levels of chemokine ligand 20 and chemokine receptor 6 in patients with sepsis: A case control study.

Background: Chemokine ligand 20 (CCL20) is a chemokine released by mainly liver and blood leucocytes. Particularly under pro-inflammatory circumstances it triggers chemotaxis of lymphocytes and dendritic cells via activating receptor chemokine receptor 6 (CCR6) that is specific to it. In experimental sepsis models, the chemokine-receptor pair has been identified as a potential pathophysiological axis affecting mortality.

Levothyroxine replacement in hypothyroid humans reduces myocardial lipid load and improves cardiac function.

Context: Hypothyroidism is a common endocrine disorder frequently accompanied by alterations in lipid metabolism, such as hypercholesterolemia and high circulating triglycerides, both risk factors for nonischemic cardiomyopathy. Rodent studies suggest that the hypothyroid state promotes cardiac lipid retention by increasing lipid uptake into cardiomyocytes while reducing fatty acid oxidation. Furthermore, increased cardiac lipid load has been linked to cardiac dysfunction.

Macrophage PTEN regulates expression and secretion of arginase I modulating innate and adaptive immune responses.

The activation of innate immune cells triggers numerous intracellular signaling pathways, which require tight control to mount an adequate immune response. The PI3K signaling pathway is intricately involved in innate immunity, and its activation dampens the expression and release of proinflammatory cytokines in myeloid cells. These signaling processes are strictly regulated by the PI3K antagonist, the lipid phosphatase, PTEN, a known tumor suppressor.

Heme oxygenase-1 drives metaflammation and insulin resistance in mouse and man.

Obesity and diabetes affect more than half a billion individuals worldwide. Interestingly, the two conditions do not always coincide and the molecular determinants of "healthy" versus "unhealthy" obesity remain ill-defined. Chronic metabolic inflammation (metaflammation) is believed to be pivotal.

Endogenous erythroid colony formation in chronic myeloid leukemia: a recurrent finding associated with persistent minimal residual disease under imatinib.

In vitro endogenous erythroid colony (EEC) formation is a common finding in BCR-ABL-negative myeloproliferative neoplasms. The aim of the present study was to determine the prevalence and the clinical significance of EEC growth in chronic myeloid leukemia (CML). Results of clonogeneic progenitor cell assays from 52 patients with newly diagnosed CML were correlated with disease characteristics at presentation and molecular response to imatinib.

Lysis matters: red cell lysis with FACS Lyse affects the flow cytometric enumeration of circulating leukemic blasts.

The whole blood lysis method has become a standard procedure to remove red cells prior to immunophenotypic analysis of leukocytes. In the present study we investigated the influence of four different lysis protocols on the flow cytometric recovery of leukemic blasts. 32 blast cells containing blood samples were stained with anti-CD45 and anti-CD34 monoclonal antibody combinations.

B-type natriuretic peptide modulates ghrelin, hunger, and satiety in healthy men.

Chronic heart failure is accompanied by anorexia and increased release of B-type natriuretic peptide (BNP) from ventricular cardiomyocytes. The pathophysiological mechanisms linking heart failure and appetite regulation remain unknown. In this study, we investigated the impact of intravenous BNP administration on appetite-regulating hormones and subjective ratings of hunger and satiety in 10 healthy volunteers.