Exposure to intrauterine inflammation leads to impaired function and altered structure in the preterm heart of fetal sheep
Intrauterine inflammation is a major contributor to preterm birth and has adverse effects on preterm neonatal cardiovascular physiology. Cardiomyocyte maturation occurs in late gestation in species such as humans and sheep. We tested the hypothesis that intrauterine inflammation has deleterious effects on cardiac function in preterm sheep which might be explained by altered cardiomyocyte proliferation and maturation. Pregnant ewes received an ultrasound-guided intra-amniotic injection of lipopolysaccharide (LPS) or saline 7 days prior to delivery at day 127 of pregnancy (term 147 days). Cardiac contractility was recorded ...
Source: Clinical Science - May 12, 2014 Category: Biomedical Science Authors: M Tare, J G. Bensley, T J. M. Moss, B E. Lingwood, M Y. Kim, S K. Barton, M Kluckow, A W. Gill, R De Matteo, R Harding, M Jane Black, H C. Parkington, G R. Polglase Source Type: research

Endoplasmic reticulum stress does not contribute to steatohepatitis in obese and insulin resistant high-fat diet fed foz/foz mice
Non-alcoholic fatty liver (steatosis) and steatohepatitis (NASH) are hepatic complications of metabolic syndrome. Endoplasmic reticulum (ER) stress is proposed as a crucial disease mechanism in obese and insulin resistant animals (such as ob/ob mice) with simple steatosis but its role in NASH remains controversial. We therefore evaluated the role of ER stress as a disease mechanism in foz/foz mice, which develop both the metabolic and the histological features that mimic human NASH. We explored ER stress markers in the liver of foz/foz mice in response to high-fat diet (HFD) after several time points. We then evaluated th...
Source: Clinical Science - April 25, 2014 Category: Biomedical Science Authors: V Legry, D M. Van Rooyen, B Lambert, C Sempoux, L Poekes, R Español-Suñer, O Molendi-Coste, Y Horsmans, G C. Farrell, I A. Leclercq Source Type: research

A novel form of the human manganese superoxide dismutase protects rat and human livers undergoing ischemia and reperfusion injuries.
In conclusion, rMnSOD represents a new and highly effective therapy to significantly upgrade liver procurement for transplantation. (Source: Clinical Science)
Source: Clinical Science - April 22, 2014 Category: Biomedical Science Authors: D Hide, M Ortega-Ribera, A Fernandez-Iglesias, C Fondevila, M Josepa Salvado, L Arola, J Carlos Garcia-Pagan, A Mancini, J Bosch, J Gracia-Sancho Source Type: research

Ectopic lipid storage in Non-Alcoholic Fatty Liver Disease is not mediated by impaired mitochondrial oxidative capacity in skeletal muscle
Non-alcoholic fatty liver disease (NAFLD), characterized by lipid deposition within the liver (intrahepatocellular lipid, IHCL), is associated with insulin resistance and the metabolic syndrome. It has been suggested that impaired skeletal muscle mitochondrial function may contribute to ectopic lipid deposition, and the associated metabolic syndrome, by altering post-prandial energy storage. To test this hypothesis, we performed a cross-sectional study of 17 patients with NAFLD (mean ± SD; age 45±11 y; BMI 31.6±3.4 kg/m2) and 18 age- and BMI-matched healthy controls (age 44±11 y; BMI 30.5±...
Source: Clinical Science - April 16, 2014 Category: Biomedical Science Authors: D J. Cuthbertson, A Irwin, C J. A. Pugh, H Jones, V Spencer Sprung, C Daousi, V L. Adams, W E. Bimson, F Shojaee-moradie, A Margot Umpleby, J P. Wilding, G J. Kemp Source Type: research

Differential bradykinin B1 and B2 receptor regulation in cell death induced by hepatic ischemia-reperfusion injury
The biological and pharmacological effects of bradykinin (BK) are mediated by two receptors: the constitutive B2 receptor (B2R) and the inducible B1 receptor (B1R). BK plays a role in the hepatic microcirculation by inducing the portal hypertensive response (PHR) via B2R, whereas des-Arg9-BK (DABK), a B1R agonist, does not elicit the response. During ischemia-reperfusion injury, important changes occur in the microcirculation, and cell death by necrosis and apoptosis is involved in poor graft function. The aim of the present study was to analyze the role of B1R and B2R in liver cell death induced by ischemia-reperfusion in...
Source: Clinical Science - April 14, 2014 Category: Biomedical Science Authors: M de Almeida Paio, M Kouyoumdjian, D Rosa Borges, M Regina Nagaoka Source Type: research

The role of bone marrow and non-bone marrow derived receptor for advanced glycation end products (RAGE) in a mouse model of diabetes-associated atherosclerosis
This study highlights the importance of both bone marrow and non-bone marrow derived RAGE in attenuating the development of DAA. (Source: Clinical Science)
Source: Clinical Science - April 11, 2014 Category: Biomedical Science Authors: C Koulis, P Kanellakis, R J. Pickering, D Tsorotes, A J. Murphy, S P. Gray, M C. Thomas, K A. M. Jandeleit-Dahm, M E. Cooper, T J. Allen Source Type: research

Effects of Folic Acid on Renal Endothelial Function in Patients with Diabetic Nephropathy: Results from a Randomized Trial
Endothelial dysfunction has been shown to promote podocyte injury and albuminuria in diabetes, highlighting the importance of the interaction between renal endothelial cells and podocytes. Folic acid (FA) improves nitric oxide synthase (NOS) function and ameliorates progression of diabetic nephropathy in animal models. We tested whether high-dose FA treatment improves renal endothelial function and albuminuria in human subjects with incipient diabetic nephropathy. Following a double-blind, randomized cross-over design, 28 patients with type 2 diabetes and albuminuria were allocated to 4-weeks treatment with placebo and hig...
Source: Clinical Science - April 11, 2014 Category: Biomedical Science Authors: M P Schneider, A Schneider, A Jumar, I Kistner, C Ott, R E Schmieder Source Type: research

Cardiomyocyte Apoptosis Contributes to Pathogenesis of Cirrhotic Cardiomyopathy in Bile Duct-Ligated Mice
Background/Aims: Cirrhotic cardiomyopathy is defined as systolic and diastolic dysfunction, electrophysiological changes, and macroscopic structural changes. However, the underlying mechanisms of this syndrome remain unclear. A possible role of myocardial apoptosis in the pathogenesis has not been previously examined. We hypothesized that dysregulation of apoptotic signaling participates in cardiac dysfunction in the cirrhotic heart. Therefore, we evaluated apoptotic pathways in the hearts of mice with chronic bile duct ligation. Methods: A cirrhotic cardiomyopathy model was induced by bile duct-ligation (BDL) in mice. Le...
Source: Clinical Science - April 9, 2014 Category: Biomedical Science Authors: S Nam, H Liu, J Z. Wang, A Y Feng, G Chu, N Merchant, S S Lee Source Type: research

Cellular aging of skeletal muscle: telomeric and free radical evidence that physical inactivity is responsible and not age
Telomeres play an essential role in maintaining chromosomal integrity in the face of physiological stressors. Although, the age-related shortening of telomere length (TL) in highly proliferative tissue, is predominantly due to the replication process, the mechanism for telomere shortening in skeletal muscle, which is minimally proliferative, is unclear. By studying TL in both the upper and lower limbs of the young (Y), old-mobile (OM), and old-immobile (OI) and by virtue of the bipedal nature of human locomotion, which declines with age, it may be possible to elucidate the mechanism responsible for cellular aging of skelet...
Source: Clinical Science - April 8, 2014 Category: Biomedical Science Authors: M Venturelli, G R. Morgan, A J. Donato, V Reese, R Bottura, C Tarperi, C Milanese, F Schena, C Reggiani, F Naro, R M. Cawthon, R S. Richardson Source Type: research

A deletion in chromosome 6q is associated with human abdominal aortic aneurysm.
Current efforts to identify the genetic contribution to abdominal aortic aneurysm (AAA) have mainly focused on the assessment of germ-line variants such as single nucleotide polymorphisms. The aim of the current study was to assess the presence of acquired chromosomal aberrations in human AAA. Microarray data of 10 biopsies obtained from the site of main AAA dilatation (AAA body) and 3 control biopsies obtained from the macroscopically non-dilated neck of the AAA (AAA neck) were initially compared to identify chromosomal aneuploidies using the ChARM software. A commonly deleted segment of chromosome bands 6 (q22.1-23.2) wa...
Source: Clinical Science - April 7, 2014 Category: Biomedical Science Authors: E Biros, C S. Moran, P J. Walker, J Cardinal, J Golledge Source Type: research

Epoxyeicosatrienoic Acid (EET) Analog Lowers Blood Pressure Through Vasodilation And Sodium Channel Inhibition
In this study, multiple structural EET analogs were synthesized based on the EET pharmacophore and vasodilator structure-activity studies. Four EET analogs with 91-119% vasodilatory activity in isolated bovine coronary artery (EC50 0.18-1.6 mM) were identified and studied for blood pressure lowering in hypertension. Two EET analogs in which the COOH group at carbon 1 of the EET pharmacophore was replaced with either an aspartic acid (EET-A) or a heterocyclic surrogate (EET-X) were administered for 14 days (10mg/kg/d i.p.). Both EET-A and EET-X lowered blood pressure in spontaneously hypertensive rat (SHR) and in angiotensi...
Source: Clinical Science - April 7, 2014 Category: Biomedical Science Authors: M Hye Khan, T S Pavlov, S V Christain, J Neckář, A Staruschenko, K M Gauthier, J H Capdevila, J R. Falck, W B Campbell, J D Imig Source Type: research

Sirtuin 1 stabilization by HuR represses TNF-{alpha} and glucose induced E-Selectin release and endothelial cell adhesiveness in vitro. Relevance to human metabolic syndrome
Chronic inflammation and hyperglycemia, typical features of metabolic diseases, trigger endothelial damage and release of E-selectin, a marker of endothelial activation.Herein, we investigated molecular pathways involved in the regulation of endothelial cell activation induced by TNF-α and high glucose. In cultured HUVECs, we studied the role of HuR, an ELAV family RNA-binding protein, and SIRT1 on E-Selectin release and cell adhesion at different glucose concentrations. HuR expression and binding to SIRT1 were also analysed ex-vivo in peripheral mononuclear cells (PBMCs) of subjects with and without metabolic syndro...
Source: Clinical Science - April 4, 2014 Category: Biomedical Science Authors: G Ceolotto, S Vigili de Kreutzenberg, A Cattelan, A S.C. Fabricio, E Squarcina, M Gion, A Semplicini, G Fadini, A Avogaro Source Type: research

Transcutaneous vagus nerve stimulation for refractory epilepsy: a randomized controlled trial
This trial was designed to test the safety and effectiveness of transcutaneous auricular vagus nerve stimulation (ta-VNS) for patients with refractory epilepsy.Pre-trial:144 patients were randomly assigned to ta-VNS group (n=98) or transcutaneous auricular non-vagus nerve stimulation (tn-VNS) control group (n=46). Treatment was conducted twice per day for 24 weeks. After 8, 16 and 24 weeks of treatment,the patients were evaluated according to the Modified Engel Scale (four classes). After 8 weeks,according to the medical ethic design, patients in tn-VNS group were switched into ta-VNS group uniquely. After 8 weeks&rs...
Source: Clinical Science - April 1, 2014 Category: Biomedical Science Authors: Rong, P., Liu, A., Zhang, J., Wang, Y., He, W., Yang, A., Li, L., Ben, H., Li, L., Liu, H., Wu, P., Liu, R., Zhao, Y., Zhang, J., Huang, F., Li, X., Zhu, B. Tags: PublishAheadOfPrint Source Type: research

Human pleural B cells regulate IFN-{gamma} production by local T and NK cells in Mycobacterium tuberculosis-induced delayed hypersensitivity reaction.
Delayed type hypersensitivity (DTH) reactions are secondary cellular immune responses, which appear 24-72 hours after antigen exposure. Tuberculous pleurisy is a common manifestation of extrapulmonary tuberculosis (TB) and is considered a human model of TH1-mediated DTH. In order to identify functional cross-talk among cellular populations sited at this inflammatory microenvironment, we analyzed phenotypic and functional features of human B cells isolated from pleural fluid (PF) of TB patients. Freshly isolated PF-B cells displayed a lower expression of CD20, CD1d and HLA-DR, and a higher expression of CD95, CD38, CD25, CX...
Source: Clinical Science - April 1, 2014 Category: Biomedical Science Authors: P Schierloh, V I Landoni, L Balboa, R M. Musella, J Castagnino, E Moraña, G C de Casado, D Palmero, M C Sasiain Source Type: research

Transcutaneous vagus nerve stimulation for refractory epilepsy: a randomized controlled trial
This trial was designed to test the safety and effectiveness of transcutaneous auricular vagus nerve stimulation (ta-VNS) for patients with refractory epilepsy.Pre-trial:144 patients were randomly assigned to ta-VNS group (n=98) or transcutaneous auricular non-vagus nerve stimulation (tn-VNS) control group (n=46). Treatment was conducted twice per day for 24 weeks. After 8, 16 and 24 weeks of treatment,the patients were evaluated according to the Modified Engel Scale (four classes). After 8 weeks,according to the medical ethic design, patients in tn-VNS group were switched into ta-VNS group uniquely. After 8 weeks&rs...
Source: Clinical Science - April 1, 2014 Category: Biomedical Science Authors: P Rong, A Liu, J Zhang, Y Wang, W He, A Yang, L Li, H Ben, L Li, H Liu, P Wu, R Liu, Y Zhao, J Zhang, F Huang, X Li, B Zhu Source Type: research

Disruption of histamine H2 receptor slows heart failure progression through reducing myocardial apoptosis and fibrosis
Histamine H2receptor (H2R) blockade has been reported to be beneficial for chronic heart failure, but the mechanisms involved are not entirely clear.Here we assessed the influences of H2R disruption on the left ventricular (LV) dysfunction and the mechanisms involved in mitochondrial dysfunction and calcineurin-mediated myocardial fibrosis.H2R knockout mice and their wildtype littermates were subjected to transverse aortic constriction (TAC) or sham surgery. The influences of H2R activation or inactivation on mitochondrial function, apoptosis and fibrosis were evaluated in cultured neonatal rat cardiomyocytes and fibroblas...
Source: Clinical Science - March 21, 2014 Category: Biomedical Science Authors: Z Zeng, L Shen, X Li, T Luo, X Wei, J Zhang, S Cao, X Huang, Y Fukushima, J Bin, M Kitakaze, D Xu, Y Liao Source Type: research

In Crohn{'}s disease fibrosis reduced expression of the miR-29 family enhances collagen expression in intestinal fibroblasts
Intestinal fibrosis with stricture formation is a complication of Crohn’s disease (CD) that may mandate surgical resection. Accurate biomarkers that reflect the relative contribution of fibrosis to an individual stricture are an unmet need in managing patients with CD. The microRNA (miR)-29 family has been implicated in cardiac, hepatic and pulmonary fibrosis. We investigated the expression of miR-29a, miR-29b and miR-29c in mucosa overlying a stricture in CD patients (SCD) paired with mucosa from non-strictured areas (NSCD). There was significant down-regulation of the miR-29 family in mucosa overlying SCD compared ...
Source: Clinical Science - March 18, 2014 Category: Biomedical Science Authors: A Nijhuis, P Biancheri, A Lewis, C L Bishop, P Giuffrida, C Chan, R M Feakins, R Poulsom, A Di Sabatino, G Roberto Corazza, T T MacDonald, J O Lindsay, A Robert Silver Source Type: research

Loss of NOX 2 (gp91phox) prevents oxidative stress and progression to advanced heart failure
Oxidative stress plays a key pathogenic role in experimental and human heart failure. However, the source of the reactive oxygen species is a key determinant of the cardiac adaptation to pathological stressors. Human dilated cardiomyopathy is associated with increased NOX2 levels, increased oxidative stress with adverse myocardial remodeling, and activation of the mitogen-activated protein kinase. Advanced heart failure in mice was also associated with increased NOX2 levels. We utilized the pressure-overload model to examine the role of NOX2 in advanced heart failure. Increased cardiomyocyte hypertrophy and myocardial fibr...
Source: Clinical Science - March 14, 2014 Category: Biomedical Science Authors: N Parajuli, V B. Patel, W Wang, R Basu, G Y. Oudit Source Type: research

Resveratrol inhibits Staphylococcus aureus-induced TLR2/MyD88/NF-{kappa}B-dependent VCAM-1 expression in human lung epithelial cells
Staphylococcus aureus (S. aureus) is the most commonly found Gram-positive bacterium in patients admitted in intensive-care units, causing septicaemia or pneumonia. S. aureus is considered to play an important role in the induction of cell adhesion molecules. Resveratrol, a compound found in the skins of red fruits, may inhibit the inflammatory signaling pathways involved in the lung diseases. Here, we reported that resveratrol reduced S. aureus-mediated vascular cell adhesion molecule-1 (VCAM-1) expression in human lung epithelial cells (HPAEpiCs) and the lungs of mice. In an in vivo study, we showed that resveratrolinhib...
Source: Clinical Science - March 12, 2014 Category: Biomedical Science Authors: I Lee, C Lin, C Hsu, M Wu, R Cho, C Yang Source Type: research

Fish oil omega-3 fatty acids partially prevent lipid induced insulin resistance in human skeletal muscle without limiting acylcarnitine accumulation
Acylcarnitine accumulation in skeletal muscle and plasma has been observed in numerous models of mitochondrial lipid overload and insulin resistance. Fish oil omega-3 polyunsaturated fatty acids (n3PUFA) are thought to protect against lipid-induced insulin resistance. The present study tested the hypothesis that addition of n3PUFA to an intravenous lipid emulsion would limit muscle acylcarnitine accumulation and reduce the inhibitory effect of lipid overload on insulin action. On three occasions, six healthy young men underwent a 6-hour euglycaemic hyperinsulinaemic clamp accompanied by intravenous infusion of saline (Cont...
Source: Clinical Science - March 10, 2014 Category: Biomedical Science Authors: F B. Stephens, B Mendis, C E. Shannon, S Cooper, C A. Ortori, D A. Barrett, P Mansell, K Tsintzas Source Type: research

Nitric Oxide Production by Monocytes in Children with OSA and Endothelial Dysfunction.
Obstructive sleep apnea (OSA) is associated with a higher risk for alterations in endothelial post-occlusive hyperemia, an eNOS-dependent response. However, since not all children manifest endothelial dysfunction (ED), we hypothesized that differences in circulating monocyte subsets and nitric oxide production may underlie the vascular phenotype in pediatric OSA. Matched pre-pubertal children with OSA with (OSAab) and without ED (OSAn), and controls (CO) were recruited. Peripheral blood mononuclear cells were subtyped into CD14+ and CD16+ cells, and nitric oxide (NO) production was assessed using flow cytometry. ED was def...
Source: Clinical Science - March 10, 2014 Category: Biomedical Science Authors: L Kheirandish-Gozal, Y Wang, R C Duggan, S Harshan Vardhan, H Tan, H Molero Ramirez, A Khalyfa, R Bhattacharjee, H PR Bandla, D Gozal Source Type: research

Comparison of Baroreflex Sensitivity to Fall and Rise in Blood Pressure Induced by the Valsalva Maneuver
The baroreflex plays a key role in human blood pressure (BP) regulation. Its efferent limb consists of a vagal and a sympathetic component. The Valsalva maneuver is widely used to quantify vagal baroreflex function (vagal baroreflex sensitivity, BRS_vagal), but most studies have focused on the R-R interval response to BP decrement, even though the subsequent response to an increment in BP is important and different. We sought to evaluate if BRS_vagal can be determined from the rise in BP during phase III-IV of the Valsalva maneuver (BRSvagalinc), to assess the association between BRSvagalinc and BRS_vagal derived from the ...
Source: Clinical Science - March 6, 2014 Category: Biomedical Science Authors: N Wada, W Singer, T L. Gehrking, D M. Sletten, J D. Schmelzer, P A. Low Source Type: research

Angiotensin 1-7/Mas-1 axis attenuates the expression and signaling of TGF-{beta}1 induced by Angiotensin II in skeletal muscle
In this study, we tested if angiotensin 1-7 (Ang 1-7), through the Mas-1 receptor, can counteract the signaling induced by Ang-II in skeletal muscle causing a decrease in the expression and further activity of TGF-β1 in skeletal muscle cells. Our results show that Ang 1-7 decreases the expression of TGF-β1 induced by Ang-II in a dose-dependent manner. In addition, we observed that Ang 1-7 prevents the increase of TGF-β1 expression induced by Ang-II, ROS production dependent on NOX, and early p38 MAPK phosphorylation. Interestingly, Ang 1-7 also prevents late p38 MAPK phosphorylation, Smad-2 phosphorylation,...
Source: Clinical Science - March 3, 2014 Category: Biomedical Science Authors: M Morales, J Abrigo, C Meneses, F Simon, F Cisternas, J Rivera, Y Vazquez, C Cabello-Verrugio Source Type: research

Angiotensin-converting enzyme-2 is subject to post-transcriptional regulation by microRNA-421
This study is the first to demonstrate ACE2 may be subject to post-transcriptional regulation and reveals a novel potential therapeutic target, miR-421, which could be exploited to modulate ACE2 expression in disease. (Source: Clinical Science)
Source: Clinical Science - February 24, 2014 Category: Biomedical Science Authors: D W. Lambert, L A. Lambert, N E. Clarke, N M. Hooper, K E. Porter, A J. Turner Source Type: research

GLP-1 at physiological concentrations recruits skeletal and cardiac muscle microvasculature in healthy humans
Muscle microvascular surface area determines substrate and hormonal exchanges between plasma and muscle interstitium. Glucagon-like peptide-1 (GLP-1) regulates glucose-dependent insulin secretion and has numerous extra-pancreatic effects, including a salutary vascular action. To examine whether GLP-1 recruits skeletal and cardiac muscle microvasculature in healthy humans, twenty-six overnight-fasted healthy adults received a systemic infusion of GLP-1 (1.2 pmol/kg/min) for 150 min. Skeletal and cardiac muscle microvascular blood volume (MBV), microvascular flow velocity (MFV) and microvascular blood flow (MBF) were determi...
Source: Clinical Science - February 20, 2014 Category: Biomedical Science Authors: S C. Subaran, M A. Sauder, W Chai, L A. Jahn, D E. Fowler, K W. Aylor, A Basu, Z Liu Source Type: research

MiR-296/Scribble axe is deregulated in human breast cancer and miR-296 restoration reduces tumor growth in vivo
MiR-296-5p is a central regulator of signalling pathways affecting development, stem cell differentiation, and cancer. We hypothesized that miR-296-5p was involved in breast cancer onset and progression possibly through regulation of its target Scribble, a polarity protein recently implicated in the acquisition of cancer stem-cell traits and in cell motility. We found that miR-296-5p levels were consistently reduced in human breast cancer tissues compared with non-neoplastic mammary parenchyma and low expression of this miRNA predicted shorter disease-free survival independently of classic clinicopathological parameters. ...
Source: Clinical Science - February 17, 2014 Category: Biomedical Science Authors: F Savi, I Forno, A Faversani, A Luciani, S Caldiera, S Gatti, P Foa, D Ricca, G Bulfamante, V Vaira, S Bosari Source Type: research

Metformin ameliorates ovariectomy-induced vascular dysfunction in non-diabetic Wistar rats
Conclusions: The pathophysiological changes observed in the mesenteric beds of OVX rats were ameliorated by metformin. If this translates to humans, metformin would have additional benefits for postmenopausal women treated with this drug for glycaemic control. (Source: Clinical Science)
Source: Clinical Science - February 13, 2014 Category: Biomedical Science Authors: P Wendell Costalonga Oliveira, G Januário de Sousa, I Facco Caliman, A Zandonadi Lamas, A Santos de Medeiros, T Uggere de Andrade, G Rodrigues de Abreu, S Gomes de Figueiredo, N Souza Bissoli Source Type: research

Smad7 inhibits Ang II-mediated hypertensive nephropathy in a mouse model of hypertension
In conclusion, Smad7 may be a therapeutic agent for Ang II-mediated hypertensive nephropathy. Inhibition of the Sp1/Smad3/NF-kB/miR-29b regulatory network may be a mechanism by which Smad7 inhibits hypertensive nephropathy. (Source: Clinical Science)
Source: Clinical Science - February 11, 2014 Category: Biomedical Science Authors: G Liu, Y Li, X R. Huang, L Wei, Y Zhang, M Feng, X Meng, H Chen, Y Shi, H Y. Lan Source Type: research

Thrombin induces ICAM-1 expression in human lung epithelial cells via c-Src/PDGFR/PI3K/Akt-dependent NF-{kappa}B/p300 activation
Up-regulation of intercellular adhesion molecule-1 (ICAM-1) is frequently implicated in lung inflammation and lung diseases, such as idiopathic pulmonary fibrosis (IPF). Thrombin has been shown to play a key role in inflammation via adhesion molecules induction, and then causes lung injury. However, the mechanisms underlying thrombin-induced ICAM-1 expression in human pulmonary alveolar epithelial cells (HPAEpiCs) remain unclear. We showed that thrombin induced ICAM-1 expression in HPAEpiCs. Pretreatment with the inhibitor of thrombin (PPACK), c-Src (PP1), PDGFR (AG1296), PI3K (LY294002), NF-κB (Bay11-7082), or p300 ...
Source: Clinical Science - February 10, 2014 Category: Biomedical Science Authors: S Cheng, I Lee, C Lin, L Hsiao, C Yang Source Type: research

Effects of a domain selective ACE inhibitor in a mouse model of chronic angiotensin II-dependent hypertension
The somatic isozyme of angiotensin I-converting enzyme (ACE) is comprised of two distinct, zinc-dependent catalytic domains with different substrate specificities for angiotensin I (cleaved selectively by the C- domain) and bradykinin (cleaved equally efficiently by both the N and C- domains). Classical ACE inhibitors (ACEI) target both domains, with side effects such as cough and angioedema being attributed, in part, to N- domain inhibition, likely through bradykinin accumulation. We questioned whether a novel C-domain selective ACEI (lisW-S) has anti-hypertensive effects without influencing bradykinin status. Ang II-depe...
Source: Clinical Science - February 10, 2014 Category: Biomedical Science Authors: D Burger, T L. Reudelhuber, A Mahajan, K Chibale, E D. Sturrock, R M. Touyz Source Type: research

Chronic oral administration of Ang-(1-7) improves skeletal muscle, autonomic, and locomotor phenotypes in muscular dystrophy
Muscular dystrophies are a group of heterogeneous genetic disorders that cause progressive muscle weakness and wasting, dilated cardiomyopathy and early mortality. There are different types of muscular dystrophies with varying etiologies but they all have a common hallmark of myofiber degeneration, atrophy and decreased mobility. Mutation in sarcoglycan-delta (Sgcd), a subunit of dystrophin glycoprotein complex, causes Limb Girdle Muscular Dystrophy 2F (LGMD2F). Previously we have reported that Sgcd deficient (Sgcd-/-) mice exhibit angiotensin II (Ang II) induced autonomic and skeletal muscle dysfunction at a young age whi...
Source: Clinical Science - February 7, 2014 Category: Biomedical Science Authors: R Sabharwal, M Z. Cicha, R D. M. Sinisterra, F B. de Sousa, R Augusto Souza Santos, M W. Chapleau Source Type: research

The kinin B1 receptor regulates muscle specific E3 ligases expression and is involved in skeletal muscle mass control
Regulation of muscle mass depends on the balance between synthesis and degradation of proteins, which is under control of different signaling pathways regulated by hormonal, neural and nutritional stimuli. Such stimuli are altered in several pathologies such as chronic obstructive pulmonary disease, diabetes, AIDS and cancer (cachexia), as well as in some conditions such as immobilization and aging (sarcopenia), leading to muscle atrophy, which represents a significant contribution to patient morbidity. The kallikrein-kinin system (KKS) is composed of the enzymes kallikreins, which generate active peptides called kinins th...
Source: Clinical Science - February 6, 2014 Category: Biomedical Science Authors: L T. Parreiras-e-Silva, R I. Reis, G A. Santos, M Pires-Oliveira, J B. Pesquero, M D. Gomes, R O. Godinho, C M. Costa-Neto Source Type: research

Chemerin reduces vascular nitric oxide - cyclic guanosine monophosphate signaling: a link to vascular dysfunction in obesity?
The adipokine chemerin has been implicated in cardiovascular complications associated with obesity and metabolic syndrome. Chemerin has direct effects in the vasculature, augmenting vascular responses to contractile stimuli. Since nitric oxide (NO)–cyclic guanosine monophosphate (cGMP) signaling plays a role in vascular dysfunction associated with obesity and metabolic syndrome, we hypothesized that chemerin induces vascular dysfunction by decreasing NO-cGMP signaling. Aortic rings from male Wistar rats (10-12 weeks-old) were incubated with chemerin (0.5 ng/mL or 5 ng/mL, 1 hour) or vehicle, and isometric tension was...
Source: Clinical Science - February 6, 2014 Category: Biomedical Science Authors: K Bianca Neves, N S. Lobato, R Alves Moreira Lopes, F P. Filgueira, C Ziliotto Zanotto, A Oliveira, R C. Tostes Source Type: research

Integrin-linked kinase: a new member of the kinases involved in hypertensive end organ damage?
Integrin-linked kinase predominantly localizes at focal adhesions to regulate actin cytoskeletal dynamics including cell migration and matrix remodeling. While recent studies suggest both physiological and pathophysiological roles of Integrin-linked kinase in the cardiovascular and renal system, its involvement in hypertensive organ dysfunctions such as those that occur in kidney had never been investigated. In this issue of Clinical Science, Alique M and co-workers have demonstrated that angiotensin II-induced renal inflammatory responses were attenuated in mice with conditional deficiency of Integrin-linked kinase, which...
Source: Clinical Science - January 31, 2014 Category: Biomedical Science Authors: T Obama, S Eguchi Source Type: research

Aliskiren limits abdominal aortic aneurysm, ventricular hypertrophy and atherosclerosis in an apolipoprotein E deficient mouse model
Conclusions: Aliskiren limits progression of AAA, VH and atherosclerosis in an ANGII-infused mouse model. (Source: Clinical Science)
Source: Clinical Science - January 30, 2014 Category: Biomedical Science Authors: S Seto, S M Krishna, C S Moran, D Liu, J Golledge Source Type: research

GdCl3 reduces hyperglycaemia through Akt/FoxO1-induced suppression of hepatic gluconeogenesis in Type 2 diabetic mice
GdCl3 (gadoliniumchloride) can reduce blood glucose, however, the underlying mechanism remains unclear. Liver gluconeogenesis is an important pathway involved in the maintenance of glucose homeostasis. The aim of the present study was to investigate the role of GdCl3 on hepatic gluconeogenesis and explore the precisemolecular mechanism. A classical Type 2 diabetic mouse model, created by exposing C57BL/6J mice to a high fat diet for 4 months, was treated with GdCl3 or saline. Bodyweight, blood glucose, and insulin sensitivity were monitored. It was observed that GdCl3 significantly reduced blood glucose levels and improved...
Source: Clinical Science - January 21, 2014 Category: Biomedical Science Authors: Q Wang, N Wang, M Dong, F Chen, Z Li, Y Chen Source Type: research

Osteopontin is up-regulated in chronic hepatitis C and is associated with cellular permissiveness for hepatitis C virus replication
Conclusions: OPN is upregulated in the liver and serum of patients with chronic HCV, and supports increased viral replication. OPN neutralization may be a novel therapeutic strategy in chronic HCV. (Source: Clinical Science)
Source: Clinical Science - January 20, 2014 Category: Biomedical Science Authors: S S. Choi, L C. Claridge, R Jhaveri, M Swiderska-Syn, P Clark, A Suzuki, T A. Pereira, Z Mi, P C. Kuo, C D. Guy, F E. L. Pereira, A Diehl, K Patel, W Syn Source Type: research

Circulating miRNA profiles provide a biomarker for severity of stroke outcomes associated with age and sex in a rat model
Small non-coding RNA (miRNA) found in circulation have been used successfully as biomarkers and mechanistic targets for chronic and acute disease. The present study investigated the impact of age and sex on microRNA expression following ischemic stroke in an animal model. Adult (6 month) and middle-aged (11-12 months) female and male rats were subject to middle cerebral artery occlusion (MCAo) using endothelin-1. Circulating miRNAs were analyzed in blood samples at 2 days and 5 days post stroke, while brain miRNA were analyzed at 5 days post stroke. While stroke-associated infarction is seen in all groups, infarct volume a...
Source: Clinical Science - January 15, 2014 Category: Biomedical Science Authors: A Selvamani, M H Williams, R C Miranda, F Sohrabji Source Type: research

Kisspeptin-10 induces endothelial cellular senescence and impaired endothelial growth
In conclusion, KP-10 suppressed endothelial growth both in-vivo and in-vitro in the present experiments. The adverse effect of KP on endothelial cells was attributable, at least in part, to the induction of cellular senescence. (Source: Clinical Science)
Source: Clinical Science - January 10, 2014 Category: Biomedical Science Authors: S Usui, Y Iso, M Sasai, T Mizukami, H Mori, T Watanabe, S Shioda, H Suzuki Source Type: research

The probiotic Lactobacillus coryniformis CECT5711 reduces vascular pro-oxydant and pro-inflammatory status in obese mice
Obesity is associated with intestine dysbiosis, and characterized by a low grade inflammatory status, which affects vascular function. In the present study we evaluated the effects of a probiotic with immunomodulatory properties, Lactobacillus coryniformis CECT5711, in obese mice fed a high fat diet (HFD). The probiotic treatment was given for 12 weeks, and it did not affect the weight evolution, although it reduced basal glycemia and insulin resistance. L. coryniformis administration to HFD-induced obese mice induced marked changes in microbiota composition and reduced the metabolic endotoxemia since it decreased the lipo...
Source: Clinical Science - January 10, 2014 Category: Biomedical Science Authors: M Toral, M Gómez-Guzmán, R Jiménez, M Romero, M Sánchez, M Utrilla, N Garrido-Mesa, M Rodriguez-Cabezas, M Olivares, J Gálvez, J Duarte Source Type: research

Maternal inheritance of circulating irisin in humans
This study aims to fill this gap. A total of 120 families (N = 254; 121 adults and 133 children) were included in this study taken from the Riyadh Biomarkers Research Program cohort. Information gathered include anthropometrics, and glycemic, lipid and adipocytokine profiles. Irisin was measured using ELISA. Examining heritability between mother and offspring the most significant heritable traits in sons included irisin (p=1.6*10-5), systolic blood pressure (p=3.6*10-4), total cholesterol (p=3.5*10-7) and LDL-cholesterol (p=1.2*10-6). Heritable traits between mother and daughter again included irisin (p
Source: Clinical Science - January 8, 2014 Category: Biomedical Science Authors: N M. Al-Daghri, O S. Al-Attas, M S. Alokail, K M. Alkharfy, M Yousef, B Vinodson, O E. Amer, A M. Alnaami, S Sabico, G Tripathi, M K. Piya, P G. McTernan, G P. Chrousos Source Type: research

Integrin Linked Kinase Plays A Key Role In The Regulation Of Angiotensin II{-}Induced Renal Inflammation
Integrin-linked kinase (ILK) is an intracellular serine/threonine kinase involved in cell-matrix interactions. ILK dysregulation has been described in chronic renal disease and modulates podocyte function and fibrosis, while data about its role in inflammation is scarce. Angiotensin II (AngII) is a proinflammatory cytokine that promotes renal inflammation. AngII blockers are renoprotective and downregulate ILK in experimental kidney disease, but the involvement of ILK in AngII actions in the kidney has not been addressed. Therefore, we investigated whether ILK signaling modulates the kidney response to systemic AngII infus...
Source: Clinical Science - January 2, 2014 Category: Biomedical Science Authors: M Alique, E Civantos, E Sanchez-Lopez, C Lavoz, S Rayego-Mateos, R Rodrigues-Diez, A Garcia-Redondo, J Egido, A Ortiz, D Rodriguez-Puyol, M Rodriguez-Puyol, M Ruiz-Ortega Source Type: research

Is it tea time for portal hypertension?
This study adds further evidence supporting that natural compounds have potential for an effective nutriceutical approach to the treatment of patients with cirrhosis of the liver. (Source: Clinical Science)
Source: Clinical Science - December 20, 2013 Category: Biomedical Science Authors: J Gracia-Sancho, J Bosch Source Type: research

Resolvin E1 promotes resolution of inflammation in a mouse model of an acute exacerbation of allergic asthma
This study provides novel evidence that RvE1 can facilitate resolution of airway inflammation in a clinically relevant model of an acute exacerbation of asthma, possibly via its effects on activated pulmonary macrophages. (Source: Clinical Science)
Source: Clinical Science - December 18, 2013 Category: Biomedical Science Authors: R P. Flesher, C Herbert, R K. Kumar Source Type: research

Gene Variations of ROCKs and Risk of Ischemic Stroke: The Women{'}s Genome Health Study
Recent animal and human studies have demonstrated the importance of RhoA/Rho-associated kinases (ROCKs) pathway in ischemic stroke (IsST). Whether the genetic variation within ROCKs-associated genes modulates IsST risk remains elusive. The association between 66 tag-SNPs (tSNPs) of 3 ROCKs-associated genes (ROCK1, ROCK2 and ARHGEF10) and incident IsST was investigated in 23,294 Caucasian female participants of the prospective Women's Genome Health Study. All were free of known cancer and cardiovascular disease at baseline. During a 15-year follow-up period, 323 participants developed a first ever IsST. Multivariable Cox re...
Source: Clinical Science - December 18, 2013 Category: Biomedical Science Authors: R Yuk-Lung Zee, Q Wang, D I Chasman, P M Ridker, J K Liao Source Type: research

Caveolin-1 is critical for abdominal aortic aneurysm formation induced by angiotensin II and inhibition of lysyl oxidase
In conclusion, Cav1 appears to play a critical role in the formation of AAA and associated endoplasmic reticulum/oxidative stress presumably through the regulation of caveolae compartmentalized signals induced by Ang II. (Source: Clinical Science)
Source: Clinical Science - December 13, 2013 Category: Biomedical Science Authors: T Takayanagi, K J. Crawford, T Kobayashi, T Obama, T Tsuji, K J. Elliott, T Hashimoto, V Rizzo, S Eguchi Source Type: research

Elevated levels of Extracellular Heat Shock Protein 72 (eHSP72) are positively correlated with insulin resistance in vivo and cause pancreatic {beta}-cell dysfunction and death in vitro
Background/aims: Extracellular heat shock protein 72 (eHSP72) is increased in the plasma of both types of diabetes and is positively correlated with inflammatory markers. Since aging is associated with a low-grade inflammation and insulin resistance (IR) we aimed to: i) analyse the concentration of eHSP72 in elderly people and determine correlation with insulin resistance and ii) determine the effects of eHSP72 on β-cell function and viability in human and rodent pancreatic β-cells. Methods: Fasting blood samples were collected from fifty older people (27♀, 23♂; 63.4±4.4 years old; BMI=25.5±2.7 ...
Source: Clinical Science - December 11, 2013 Category: Biomedical Science Authors: M Krause, K Keane, J Rodrigues-Krause, D Crognale, B Egan, G De Vito, C Murphy, P Newsholme Source Type: research

Circulating PCSK9 is a strong determinant of plasma triglycerides and total cholesterol in homozygous carriers of apolipoprotein {epsilon}2
In this study we investigated the role of circulating proprotein convertase subtilisin kexin type 9 (PCSK9), an important regulator of LDL receptor expression, in the development of this hyperlipidemic phenotype. Methods: In an observational study, plasma PCSK9 was measured in homozygous carriers of apolipoprotein ε2 (ε2/ε2; n=12), normal controls (n=72) and hypertriglyceridemic patients with familial combined hyperlipidemia (FCHL; n=38), who served as a hyperlipidemic reference group. Cholesterol, triglycerides and apolipoprotein B content in VLDL and LDL particles was determined by ultracentrifug...
Source: Clinical Science - December 6, 2013 Category: Biomedical Science Authors: M C.G.J. Brouwers, M M. J. van Greevenbroek, R J. Konrad, J S. Troutt, N C. Schaper, C D.A. Stehouwer Source Type: research

Identification of four novel serum protein biomarkers in sepsis patients encoded by target genes of sepsis-related microRNAs
The goal of this study was to identify novel protein biomarkers from the target genes of six serum miRNAs that we identified previously in sepsis patients. The target genes were predicted by bioinformatics analysis; the levels of the respective proteins in the sera of sepsis patients were detected by enzyme-linked immunosorbent assays (ELISA). Activin A receptor, type IIA (ACVR2A), Forkhead box O1 (FOXO1), Indian hedgehog (IHH), Serine/threonine kinase 4 (STK4), and Dual specificity phosphatase 3 (DUSP3) were predicted to be the targets of the six miRNAs, and their encoded proteins were used for biomarker identification. Levels of ACVR2A (p
Source: Clinical Science - December 5, 2013 Category: Biomedical Science Authors: H Wang, B Wang, P Zhang, J Deng, Z Zhao, X Zhang, K Xiao, D Feng, Y Jia, Y Liu, L Xie Source Type: research

Everolimus is a potent inhibitor of activated hepatic stellate cell functions in vitro and in vivo, while demonstrating anti-angiogenic activities
Progression of liver fibrosis to hepatocellular carcinoma (HCC) is a very complex process which involves several pathological phenomenon including hepatic stellate cells activation, inflammation, fibrosis and angiogenesis. Therefore, inhibiting multiple pathological processes using a single drug can be an effective choice to curb the progression of HCC. In the present study, we used the mTOR inhibitor Everolimus to observe its effect on in vitro activation of hepatic stellate cells and angiogenesis. Our data demonstrated that Everolimus treatment blocked the functions of the immortalized human activated hepatic stellate ce...
Source: Clinical Science - November 28, 2013 Category: Biomedical Science Authors: A Piguet, S Majumder, U Maheshwari Balaguru, R Manjunathan, U Saran, S Chatterjee, J Dufour Source Type: research