Connective tissue growth factor expression and Smad signaling during mouse heart development and myocardial infarction.

Connective tissue growth factor (CTGF) is reported to be a target gene of transforming growth factor beta (TGFbeta) and bone morphogenetic protein (BMP) in vitro. Its physiological role in angiogenesis and skeletogenesis during mouse development has been described recently. Here, we have mapped expression of CTGF mRNA during mouse heart development, postnatal adult life, and after experimental myocardial infarction. Furthermore, we investigated the relationship between CTGF and the BMP/TGFbeta signaling pathway in particular during heart development in mutant mice. Postnatally, CTGF expression in the heart became restricted to the atrium. Strikingly, 1 week after myocardial infarction, when myocytes have disappeared from the infarct zone, CTGF and TGFbeta expression as well as activated forms of TGFbeta but not BMP, Smad effector proteins are colocalized exclusively in the fibroblasts of the scar tissue, suggesting possible cooperation between CTGF and TGFbeta during the pathological fibrotic response.     

Functionalization of Polycaprolactone Electrospun Osteoplastic Scaffolds with Fluorapatite and Hydroxyapatite Nanoparticles: Biocompatibility Comparison of Human Versus Mouse Mesenchymal Stem Cells

A capability for effective tissue reparation is a living requirement for all multicellular organisms. Bone exits as a precisely orchestrated balance of bioactivities of bone forming osteoblasts and bone resorbing osteoclasts. The main feature of osteoblasts is their capability to produce massive extracellular matrix enriched with calcium phosphate minerals. Hydroxyapatite and its composites represent the most common form of bone mineral providing mechanical strength and significant osteoinductive properties. Herein, hydroxyapatite and fluorapatite functionalized composite scaffolds based on electrospun polycaprolactone have been successfully fabricated. Physicochemical properties, biocompatibility and osteoinductivity of generated matrices have been validated. Both the hydroxyapatite and fluorapatite containing polycaprolactone composite scaffolds demonstrated good biocompatibility towards mesenchymal stem cells. Moreover, the presence of both hydroxyapatite and fluorapatite nanoparticles increased scaffolds’ wettability. Furthermore, incorporation of fluorapatite nanoparticles enhanced the ability of the composite scaffolds to interact and support the mesenchymal stem cells attachment to their surfaces as compared to hydroxyapatite enriched composite scaffolds. The study of osteoinductive properties showed the capacity of fluorapatite and hydroxyapatite containing composite scaffolds to potentiate the stimulation of early stages of mesenchymal stem cells’ osteoblast differentiation. Therefore, polycaprolactone based composite scaffolds functionalized with fluorapatite nanoparticles generates a promising platform for future bone tissue engineering applications.     

The influence of low-dose atorvastatin on lipid levels and endothelial vascular function in patients with significant coronary artery stenosis

BACKGROUND: Hyperlipidaemia is a well-established risk factor of the progression of coronary artery disease (CAD). Statins such as atorvastatin, as lipid-lowering agents, can not only normalise serum lipid levels, but also may improve endothelial function, reduce vascular inflammation and enhance plaque stability. AIM: To evaluate the efficacy of a low-dose atorvastatin regimen (10 mg daily) in patients with CAD. METHODS: Seventy-nine patients with stable angina of II or III functional class and angiographically significant stenosis of coronary arteries (>70%) entered a 12-week treatment period with atorvastatin 10 mg/day. Lipid profile, which included total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG) were assessed at baseline and after treatment at week 12. In addition, flow-mediated vasodilatation (FMD) and nitrate-induced dilation (NID) of the brachial artery were measured before and after treatment. RESULTS: Among 79 patients included in the study, in 54 (68%) the target TC value <5.0 mmol/l, and in 51 (65%) the LDL-C level <3.0 mmol/l were achieved. Atorvastatin decreased TC level by 31% (p<0.01), LDL-C level by 35% (p<0.01), TG level by 23% (p<0.01) and increased HDL-C level by 8% (p<0.01). FMD was increased by 61 % (p<0.01) and normalised in 88% of patients after 3-month therapy of atorvastatin. NID was increased by 16% (p<0.05). CONCLUSION: Low-dose treatment with atorvastatin (10 mg daily) is effective in reducing blood lipids and is associated with the improvement of endothelial function in patients with CAD.     

Cholesterol enriched diet suppresses ATF6 and PERK and upregulates the IRE1 pathways of the unfolded protein response in spontaneously hypertensive rats: Relevance to pathophysiology of atherosclerosis in the setting of hypertension

Many studies have been dedicated to hypertension and hypercholesterolemia, as they are the primary conditions that influence the unfolded protein response (UPR). However, the concurrent effects of these two factors are unknown. Our research used spontaneously hypertensive rats (SHR) fed a cholesterol enriched diet (CED) as model of atherosclerosis formation to discover what effect the simultaneous actions of hypertension and hypercholesterolemia have on the UPR. The combination of hypertension and consumption of a CED (not the CED alone) caused the formation of early atherosclerotic features. Both increased expression of the CCAAT-enhancer-binding protein (CHOP) and the insulin induced gene 1 (INSIG1), which is the target gene of the sterol regulatory element-binding protein 1-c (SREBP1-c), and decreased expression of the spliced x-box binding protein1 (sXBP1) mRNA were observed in the SHR fed a CED. Cholesterol overload strongly suppressed glucose regulated protein 78 (GRP78), glucose regulated protein 94 (GRP 94), and the expression of CHOP and INSIG1 mRNA in both normotensive and hypertensive rats. Unlike other UPR factors, the sXBP1 mRNA expression was strongly downregulated in SHR fed a normal diet but upregulated in those fed a CED. The changes to UPR in the SHR fed a CED were associated with improvement of the initially impaired heart function of the rats.     

HIV and hepatitis C virus infections among hanka injection drug users in central Ukraine: a cross-sectional survey

Background  

Ukraine has experienced an increase in injection drug use since the 1990s. An increase in HIV and hepatitis C virus infections has followed, but not measures of prevalence and risk factors. The purposes of this study are to estimate the prevalence of HIV, HCV, and co-infection among injection drug users (IDUs) in central Ukraine and to describe risk factors for HIV and HCV.     

Intermetallic Phases Identification and Diffusion Simulation in Twin-Roll Cast Al-Fe Clad Sheet

Aluminium steel clad materials have high potential for industrial applications. Their mechanical properties are governed by an intermetallic layer, which forms upon heat treatment at the Al-Fe interface. Transmission electron microscopy was employed to identify the phases present at the interface by selective area electron diffraction and energy dispersive spectroscopy. Three phases were identified: orthorhombic Al₅Fe₂, monoclinic Al₁₃Fe₄ and cubic Al₁₉Fe₄MnSi₂. An effective interdiffusion coefficient dependent on concentration was determined according to the Boltzmann–Matano method. The highest value of the interdiffusion coefficient was reached at the composition of the intermetallic phases. Afterwards, the process of diffusion considering the evaluated interdiffusion coefficient was simulated using the finite element method. Results of the simulations revealed that growth of the intermetallic phases proceeds preferentially in the direction of aluminium.