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Antenatal imatinib treatment reduces pulmonary vascular remodeling in a rat model of congenital diaphragmatic hernia

The pathophysiology of congenital diaphragmatic hernia (CDH) is constituted by pulmonary hypoplasia and pulmonary hypertension (PH). We previously reported successful treatment with imatinib of a patient with CDH. This study examines the effect of antenatal imatinib administration on the pulmonary vasculature in a rat model of CDH. Pregnant rats were given nitrofen to induce CDH. Controls were giv

Heparan sulfate in perlecan promotes mouse atherosclerosis : Roles in lipid permeability, lipid retention, and smooth muscle cell proliferation

Heparan sulfate (HS) has been proposed to be antiatherogenic through inhibition of lipoprotein retention, inflammation, and smooth muscle cell proliferation. Perlecan is the predominant HS proteoglycan in the artery wall. Here, we investigated the role of perlecan HS chains using apoE null (ApoE0) mice that were cross-bred with mice expressing HS-deficient perlecan (Hspg2 Δ3/Δ3). Morphometry of cr

Reduced perlecan expression and accumulation in human carotid atherosclerotic lesions

Heparan sulfate in the extracellular matrix of the artery wall has been proposed to possess anti-atherogenic properties by interfering with lipoprotein retention, suppression of inflammation, and inhibition of smooth muscle cell growth. Previously, the amount of heparan sulfate in atherosclerotic lesions from humans and animals has been shown to be reduced but the identity or identities of the hep

Increased Intimal Hyperplasia and Smooth Muscle Cell Proliferation in Transgenic Mice with Heparan Sulfate-Deficient Perlecan

Smooth muscle cell (SMC) proliferation is a critical process in vascular disease. Heparan sulfate (HS) proteoglycans inhibit SMC growth, but the role of endogenous counterparts in the vessel wall in control of SMC function is not known in detail. Perlecan is the major HS proteoglycans in SMC basement membranes and in vessel wall extracellular matrix (ECM). In this study, transgenic mice with HS-de

Effect of NGF, BDNF, bFGF, aFGF and cell density on NPY expression in cultured rat dorsal root ganglion neurones

The effect of neurotrophic factors on neuropeptide Y (NPY) expression was studied in adult rat dispersed dorsal root ganglion (DRG) cultures. Nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), acidic fibroblast growth factor (aFGF) or basic FGF was included in the culture medium during incubation for 72 h. In untreated cultures, around 18% of all neurones (visualized by antibodie

Inhibition of rat smooth muscle cell adhesion and proliferation by non-anticoagulant heparins

Heparin is a well established growth inhibitor of arterial smooth muscle cells (SMCs) both in animal models and in vitro. Even though the cellular mechanisms involved in the anti-proliferative properties of heparin are being resolved, the structural requirements for the biological effects of heparin are not known in detail. Here, we have studied the effect of chemically modified heparins of differ

Fibronectin promotes cell cycle entry in smooth muscle cells in primary culture

Smooth muscle cell proliferation after arterial injury is regulated by growth factors and components of the extracellular matrix. We have previously demonstrated that fibronectin promotes a phenotypic modulation of freshly isolated rat smooth muscle cells from a contractile to a synthetic phenotype in primary culture and supports the ability of the cells to respond to growth factors. Here, we ana

Control of smooth muscle cell proliferation - The role of the basement membrane

In atherogenesis and in response to vessel injury, arterial smooth muscle cells (SMCs) are activated from a quiescent, differentiated state into an actively proliferating and synthetic phenotype which migrate into the intima where the cells participate in the formation of a fibrous plaque or intimal hyperplasia. The mechanisms involved in the control of SMC function are not clear and no preventive

Perlecan inhibits smooth muscle cell adhesion to fibronectin : Role of heparan sulfate

Smooth muscle cell migration, proliferation, and deposition of extracellular matrix are key events in atherogenesis and restenosis development. To explore the mechanisms that regulate smooth muscle cell function, we have investigated whether perlecan, a basement membrane heparan sulfate proteoglycan, modulates interaction between smooth muscle cells and other matrix components. A combined substra

Increased EZH2 expression in prostate cancer is associated with metastatic recurrence following external beam radiotherapy

Background: Enhancer of zeste 2 (EZH2) promotes prostate cancer progression. We hypothesized that increased EZH2 expression is associated with postradiotherapy metastatic disease recurrence, and may promote radioresistance. Methods: EZH2 expression was investigated using immunohistochemistry in diagnostic prostate biopsies of 113 prostate cancer patients treated with radiotherapy with curative int

Delayed cord clamping was not associated with an increased risk of hyperbilirubinaemia on the day of birth or jaundice in the first 4 weeks

AIM: Our aim was to investigate the effects of timing of cord clamping on the risk of hyperbilirubinaemia.METHODS: We recruited 540 normal vaginal deliveries at the Paropakar Maternity and Women's Hospital in Kathmandu, Nepal, from 2 October to 21 November 2014. They were randomised into two groups: 257/270 were cord clamped within 60 seconds and 209/270 after 180 seconds. Transcutaneous bilirubin

FoxA1 directs the lineage and immunosuppressive properties of a novel regulatory T cell population in EAE and MS

The defective generation or function of regulatory T (T reg) cells in autoimmune disease contributes to chronic inflammation and tissue injury. We report the identification of FoxA1 as a transcription factor in T cells that, after ectopic expression, confers suppressive properties in a newly identified T reg cell population, herein called FoxA1 + T reg cells. FoxA1 bound to the Pdl1 promoter, indu

Antiinflammatory properties of a peptide derived from interleukin-4

Interleukin-4 (IL-4) is a potent antiinflammatory cytokine. However its use in the clinic is hampered by side effects. We here describe the identification of a novel synthetic peptide, termed Ph8, derived from α-helix C of IL-4, which interacts with IL-4 receptor α (IL-4Rα). Employing various cultured genetically engineered cell lines and primary lymphocytes, surface plasmon resonance, qPCR, ELISA

Transcription factor AP-4 is a ligand for immunoglobulin-κ promoter E-box elements

Immunoglobulin (Ig)-κ promoters from humans and mice share conserved sequences. The octamer element is common to all Ig promoters and pivotal for their function. However, other conserved sequence motifs, that differ between lg variable gene families, are required for normal promoter function. These conserved motifs do not stimulate transcription in the absence of an octamer. One example is an E-bo

Exclusive electroproduction of \phi mesons at 4.2 GeV

We studied the exclusive reaction e→pe′p′φ using the →φK+K− decay mode. The data were collected using a 4.2 GeV incident electron beam and the CEBAF Large Acceptance Spectrometer (CLAS) at the Thomas Jefferson National Accelerator Facility. Our experiment covers the range in Q2 from 0.7 to 2.2 GeV2, and W from 2.0 to 2.6 GeV. Taken together with all previous data, we find a consistent picture of φ

Climate mitigation comparison of woody biomass systems with the inclusion of land-use in the reference fossil system

While issues of land-use have been considered in many direct analyses of biomass systems, little attention has heretofore been paid to land-use in reference fossil systems. Here we address this limitation by comparing forest biomass systems to reference fossil systems with explicit consideration of land-use in both systems. We estimate and compare the time profiles of greenhouse gas (GHG) emissio

A systems biology approach to investigate the effect of pH-induced gene regulation on solvent production by Clostridium acetobutylicum in continuous culture

Background: Clostridium acetobutylicum is an anaerobic bacterium which is known for its solvent-producing capabilities, namely regarding the bulk chemicals acetone and butanol, the latter being a highly efficient biofuel. For butanol production by C. acetobutylicum to be optimized and exploited on an industrial scale, the effect of pH-induced gene regulation on solvent production by C. acetobutyli