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Clinical Science (1979-)

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https://www.readbyqxmd.com/read/28424290/skin-derived-precursors-from-human-subjects-with-type-2-diabetes-yield-dysfunctional-vascular-smooth-muscle-cells
#1
Sarah Katherina Steinbach, Terrence M Yau, Maral Ouzounian, Husam Abdel-Qadir, Mark Chandy, Thomas Waddell, Mansoor Husain
Objective: Few methods enable molecular and cellular studies of vascular aging or type-2 diabetes (T2D). Here we report a new approach to studying human vascular smooth muscle cell (VSMC) pathophysiology by examining VSMCs differentiated from progenitors found in skin. Approach and Results: Skin-derived precursors (SKPs) were cultured from biopsies (N=164, ~1 cm(2)) taken from the edges of surgical incisions of older adults (N=158; males 72%; mean age 62.7±13 years) undergoing cardiothoracic surgery, and differentiated into VSMCs at high efficiency (>80% yield)...
April 19, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28420676/the-association-between-etanercept-serum-concentration-and-psoriasis-severity-is-highly-age-dependent
#2
Iris Detrez, Kristel Van Steen, Siegfried Segaert, Ann Gils
The association between etanercept serum concentration and psoriasis disease severity is poorly investigated and currently etanercept serum concentration monitoring aiming to optimize psoriasis treatment lacks evidence. In this prospective study, we investigated the relation between etanercept exposure and disease severity via measuring etanercept concentrations at five consecutive time points in 56 psoriasis patients. Disease severity assessments included the Psoriasis Area and Severity Index (PASI), Body Surface Area (BSA) and Physician Global Assessment (PGA), and etanercept and anti-etanercept antibody concentrations were determined every three months for a period of one year...
April 18, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28404768/dj-1-overexpression-restores-ischaemic-post-conditioning-mediated-cardioprotection-in-diabetic-rats-%C3%AF-role-of-autophagy
#3
Bin Zhou, Shaoqing Lei, Rui Xue, Yan Leng, Zhengyuan Xia, Zhong-Yuan Xia
IPO (Ischaemic post-conditioning) is a promising method of alleviating myocardial IR (ischaemia -reperfusion) injury; however, IPO-mediated cardioprotection is lost in diabetic hearts via mechanisms that remain largely unclear. We hypothesized that decreased cardiac expression of DJ-1, a positive modulator of autophagy, compromises the effectiveness of IPO-induced cardioprotection in diabetic rats. Diabetic rats subjected to myocardial IR (30 min of coronary artery occlusion followed by 120 min of reperfusion) exhibited more severe myocardial injury, less cardiac autophagy, lower DJ-1 expression and AMPK (adenosine monophosphate-activated protein kinase)/mTOR (mammalian target of rapamycin) pathway activity than non-diabetic rats...
April 12, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28385735/prior-exercise-and-standing-as-strategies-to-circumvent-sitting-induced-leg-endothelial-dysfunction
#4
Takuma Morishima, Robert M Restaino, Lauren K Walsh, Jill A Kanaley, Jaume Padilla
We have previously shown that local heating or leg fidgeting can prevent prolonged sitting-induced leg endothelial dysfunction. However, whether physical activity prevents subsequent sitting-induced leg endothelial dysfunction remains unknown. Herein, we tested the hypothesis that sitting-induced leg endothelial dysfunction would be prevented by prior exercise. We also examined if, in the absence of exercise, standing is an effective alternative strategy to sitting for conserving leg endothelial function. Fifteen young healthy subjects completed three randomized experimental trials: 1) sitting without prior exercise; 2) sitting with prior exercise; and 3) standing without prior exercise...
April 6, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28381600/increased-neutrophil-gelatinase-associated-lipocalin-ngal-promotes-airway-remodelling-in-chronic-obstructive-pulmonary-disease
#5
Yujie Wang, Man Jia, Xiaoyi Yan, Limin Cao, Peter J Barnes, Ian M Adcock, Mao Huang, Xin Yao
Airway remodelling is an important component of chronic obstructive pulmonary disease (COPD). Neutrophil gelatinase-associated lipocalin (NGAL) from neutrophils may drive COPD epithelial-mesenchymal transition (EMT). NGAL expression was quantified in the lungs of COPD patients and bronchoalveolar lavage fluid (BALF) of ozone-treated mice. Reticular basement membrane (RBM) thickness and E-cadherin and α-smooth muscle actin (α-SMA) expression were determined in mice airways. Effects of cigarette smoke extract (CSE) and inflammatory factors on NGAL expression in human neutrophils as well as the effects of NGAL on airway structural cells was assessed...
April 5, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28364044/high-serum-thrombospondin-1-concentration-is-associated-with-slower-abdominal-aortic-aneurysm-growth-and-deficiency-promotes-angiotensin-ii-induced-aneurysm-in-mice
#6
Smriti M Krishna, Saiwang Seto, Roby Jose, Jiaze Li, Joseph V Moxon, Paula Clancy, David J Crossman, Paul E Norman, Theophilus I Emeto, Jonathan Golledge
Abdominal aortic aneurysm (AAA) is a common age-related vascular disease characterized by progressive weakening and dilatation of the aortic wall. Thrombospondin-1 (TSP-1; gene Thbs1) is a member of the matricellular protein family important in the control of extracellular matrix remodeling. In this study, the association of serum TSP-1 concentration with AAA progression was assessed in 276 men that underwent repeat ultrasound for a median 5.5 years. AAA growth was negatively correlated with serum TSP-1 concentration ( Spearman's rho (-)0...
March 31, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28360194/neuronal-nitric-oxide-synthase-derived-hydrogen-peroxide-effect-in-grafts-used-in-human-coronary-bypass-surgery
#7
Patrick Wander Endlich, Rosária Dias Aires, Roberta Lins Gonçalves, Eduardo Damasceno Costa, Janaína de Paula Arantes Ângelo, Lucas Ferreira Alves, Rafaela Fernandes da Silva, Bruno Almeida Rezende, Steyner F Cortes, Virgínia S Lemos
Recently, H2O2 has been identified as the endothelium-dependent hyperpolarizing factor (EDHF), which mediates flow-induced dilation in human coronary arteries. Neuronal nitric oxide synthase (nNOS) is expressed in the cardiovascular system and besides NO, generates H2O2 The role of nNOS-derived H2O2 in human vessels is so far unknown. The present study aimed at investigating the relevance of nNOS/H2O2 signaling in human internal mammary artery (IMA) and saphenous vein (SV), the major conduits used in coronary artery bypass grafting...
March 30, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28360193/a-role-for-galectin-3-in-the-development-of-early-molecular-alterations-in-short-term-aortic-stenosis
#8
Vanessa Arrieta, Ernesto Martínez-Martínez, Jaime Ibarrola, Virginia Alvarez, Rafael Justo Sádaba, Amaia García-Peña, Amaya Fernández-Celis, Victoria Cachofeiro, Patrick Rossignol, Natalia Lopez-Andres
Aortic stenosis (AS) is characterized by pressure overload and causes left ventricular (LV) fibrosis and inflammation, two mechanisms which finally lead to cardiac dysfunction. Galectin-3 (Gal-3), a β-galactoside-binding lectin, promotes cardiac remodeling. We herein investigated the role of Gal-3 in LV remodeling in patients with AS and the effects of Gal-3 blockade in rats subjected to short-term (6-week) supravalvular aortic banding (AS group). Myocardial biopsies were obtained from 25 patients with severe AS referred for aortic valve replacement and from necropsies of 11 cardiovascular disease-free control subjects...
March 30, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28348005/vascular-basement-membrane-alterations-and-%C3%AE-amyloid-accumulations-in-an-animal-model-of-cerebral-small-vessel-disease
#9
Friederike Held, Alan W J Morris, Daniel Pirici, Solveig Niklass, Matthew M G Sharp, Cornelia Garz, Anne Assmann, Hans-Jochen Heinze, Frank Schreiber, Roxana Octavia Carare, Stefanie Schreiber
Non-amyloid cerebral small vessel disease (CSVD) and cerebral amyloid angiopathy (CAA) may be interrelated by the damaged basement membranes (BMs) and extracellular matrix changes of small vessels, resulting in a failure of β-amyloid (Aβ) transport and degradation. We analysed BM changes and the pattern of deposition of Aβ in the walls of blood vessels in spontaneously hypertensive stroke-prone rats (SHRSP), a non-transgenic CSVD model. In 45 SHRSP and 38 Wistar rats aged 18 to 32 weeks 1) the percentage area immunostained for vascular collagen IV and laminin was quantified, 2) the capillary BM thickness as well as endothelial and pericyte pathological changes were analysed using transmission electron microscopy (TEM) and 3) the presence of vascular Aβ was assessed...
March 27, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28341661/vascular-endothelial-growth-factor-a165b-ameliorates-outer-retinal-barrier-and-vascular-dysfunction-in-the-diabetic-retina
#10
Nikita Ved, Richard P Hulse, Samuel M Bestall, Lucy F Donaldson, James W Bainbridge, David Bates
Diabetic retinopathy (DR) is one of the leading causes of blindness in the developed world. Characteristic features of DR are retinal neurodegeneration, pathological angiogenesis and breakdown of both the inner and outer retinal barriers of the retinal vasculature and RPE-choroid respectively. Vascular endothelial growth factor-A (VEGF), a key regulator of angiogenesis and permeability, is the target of most pharmacological interventions of DR. VEGF-A can be alternatively spliced at exon 8 to form 2 families of isoforms, pro- and anti-angiogenic...
March 24, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28341660/the-noncoding-rna-linc-adamts5-cooperates-with-rreb1-to-protect-from-intervertebral-disc-degeneration-through-inhibiting-adamts5-expression
#11
Kun Wang, Yu Song, Wei Liu, Xinghuo Wu, Yukun Zhang, Shuai Li, Liang Kang, Ji Tu, Kangcheng Zhao, Wenbin Hua, Cao Yang
Previous studies have indicated the important roles of ADAMTS5 in intervertebral disc degeneration. However, the mechanisms that regulate ADAMTS5 expression in nuclear pulposus (NP) cells remain largely unknown. Evidence suggests that intergenic transcription may be associated with genes that encode transcriptional regulators. Here, we identified a long intergenic noncoding RNA, linc-ADAMTS5, that was transcribed in the opposite direction of ADAMTS5. In this study, through mining computational algorithm programs, and public available data sets, we identified Ras responsive element binding protein 1 (RREB1) as a crucial transcription factor regulating the expression of ADAMTS5 in NP cells...
March 24, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28341659/chronic-microaspiration-of-bile-acids-induces-lung-fibrosis-through-multiple-mechanisms-in-rats
#12
Bi Chen, Wen Jie You, Xue Qing Liu, Shan Xue, Hui Qin, Han Dong Jiang
Gastroesophageal reflux (GER) and microaspiration of duodenogastric refluxate have been recognized as a risk factor for pulmonary fibrosis. Recent evidence implicates that bile acid microaspiration may contribute to the development of lung fibrosis. However, the molecular evidences are scarce and the underlying mechanisms remain to be elucidated. We have recently demonstrated that bile acids induce activation of alveolar epithelial cells and lung fibroblasts in vitro In this study, a rat model of bile acid microaspiration was established by weekly intratracheal instillation of three major bile acids including chenodeoxycholic acid (CDCA), deoxycholic acid (DCA) and lithocholic acid (LCA) ...
March 24, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28325855/pretreatment-with-aldh2-agonist-alda-1-reduces-intestinal-injury-induced-by-ischemia-and-reperfusion-in-mice
#13
Qiankun Zhu, Guizhen He, Jie Wang, Yukang Wang, Wei Chen
Many studies demonstrate that activation of aldehyde dehydrogenase 2 (ALDH2) is protective against oxidative stress via detoxification of cytotoxic aldehydes and could attenuate cardiac, cerebral, lung, and renal ischemia reperfusion (IR) injuries. However, the effect of ALDH2 in intestinal IR is unknown. This study was to determine whether ALDH2 agonist, Alda-1, could alleviate intestinal injury after gut IR. In a mice model of intestinal IR injury, histological grading, proinflammatory cytokines, oxidative stress, cellular apoptosis, chemokine contents, ALDH2 activity, 4-HNE and MDA were evaluated...
March 21, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28320782/diabetes-confers-in-vitro-calcific-potential-on-serum-which-associates-with-in-vivo-vascular-calcification
#14
Ashish Patidar, Dhruv K Singh, Shori Thakur, Peter Winocour, Ken Farrington, Anwar Baydoun
Although vascular calcification (VC) is prevalent in type 2 diabetes (T2DM), underlying mechanisms remain unclear. Neither is it known whether T2DM confers calcific potential (CP) to serum, enabling it to induce VC outside the disease milieu. We therefore investigated the CP of serum from controls and subjects with T2DM with and without in vivo VC . Samples from 20 healthy controls and 45 age- and sex-matched patients with T2DM with MDRD-eGFR>60mL min(-1) were analysed for CP using rat aortic smooth muscle cells in vitro CT scans of femoral arteries identified individuals with in vivo calcification...
March 20, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28246131/the-effect-of-cortisol-in-rat-steatotic-and-non-steatoticliver-transplantation-from-brain-dead-donors
#15
Mónica Bibiana Jiménez-Castro, Elsa Negrete-Sánchez, Araní Casillas-Ramírez, Jose Gulfo, Ana I Álvarez-Mercado, Maria Eugenia Cornide-Petronio, Jordi Gracia-Sancho, Juan Rodés, Carmen Peralta
In this study, we examined the effects of cortisol on steatotic and non-steatotic liver grafts from brain-dead donors and characterized the underlying mechanisms involved. Non-steatotic liver grafts showed reduced cortisol and increased cortisone levels in association with upregulation of enzymes that inactivate cortisol. Conversely, steatotic liver grafts exhibited increased cortisol and reduced cortisone levels. The enzymes involved in cortisol generation were overexpressed, and those involved in cortisol inactivation or clearance were downregulated in steatotic liver grafts...
February 28, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28232511/inhibition-of-p66shc-mediated-mitochondrial-apoptosis-via-targeting-prolyl-isomerase-pin1-attenuates-intestinal-ischemia-reperfusion-injury-in-rats
#16
Dongcheng Feng, Jihong Yao, Guangzhi Wang, Zhenlu Li, Guo Zu, Yang Li, Fuwen Luo, Shili Ning, Wasim Qasim, Zhao Chen, Xiaofeng Tian
Intestinal epithelial oxidative stress and apoptosis constitute key pathogenic mechanisms underlying intestinal ischemia/reperfusion (I/R) injury. We previously reported that the adaptor p66Shc-mediated pro-apoptotic pathway was activated after intestinal I/R. However, the upstream regulators of the p66Shc pathway involved in intestinal I/R remain to be fully identified. Here, we focused on the role of a prolyl-isomerase, Pin1, in the regulation of p66Shc activity during intestinal I/R. Intestinal I/R was induced in rats by superior mesenteric artery (SMA) occlusion...
February 23, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28196857/deletion-of-hypoxia-inducible-factor-1%C3%AE-in-myeloid-lineage-exaggerates-angiotensin-ii-induced-formation-of-abdominal-aortic-aneurysm
#17
Yusuke Takahara, Tomotake Tokunou, Hiroshi Kojima, Yoshitaka Hirooka, Toshihiro Ichiki
Hypoxia-inducible factor (HIF)-1α is a transcription factor that regulates various genes responding to hypoxic conditions. We previously reported that myeloid-specific activation of HIF-1α had protective effects on hypertensive cardiovascular remodeling in mice. However the role of myeloid lineage HIF-1α in the development of abdominal aortic aneurysm (AAA) has not been determined. Myeloid-specific HIF-1α knockout (HIF-1KO) mice were created using a Cre-lox recombination system in the background of apolipoprotein E-deficient mice...
February 14, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28196856/vardenafil-reduces-macrophage-pro-inflammatory-overresponses-in-cystic-fibrosis-through-pde5-and-cftr-dependent-mechanisms
#18
Sabrina Noel, Nadtha Panin, Mathilde Beka, Barbara Dhooghe, Francois Huaux, Teresinha Leal
Chronic inflammation that progressively disrupts the lung tissue is a hallmark of Cystic Fibrosis (CF). In mice, vardenafil, an inhibitor of phosphodiesterase type 5 (PDE5), restores transepithelial ion transport and corrects mislocalization of the most common CF mutation, F508del-CFTR. It also reduces lung pro-inflammatory responses in mice and in patients with CF. To test the hypothesis that macrophages are target effector cells of the immunomodulatory effect of vardenafil, we isolated lung macrophages from mice homozygous for the F508del mutation or invalidated for the cftr gene and from their corresponding wild-type littermates...
February 14, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28188238/vmp1-related-autophagy-induced-by-fructose-rich-diet-in%C3%A2-%C3%AE-cells-it-s-prevention-by-incretins
#19
Bárbara Maiztegui, Verónica Boggio, Carolina Lisi Román, Luis Emilio Flores, Héctor Del Zotto, Alejandro Ropolo, Daniel Grasso, María Inés Vaccaro, Juan José Gagliardino
Aim : To demonstrate the role of autophagy and incretins on fructose-induced alteration in β-cell mass and function. Methods : Normal Wistar rats were fed (3 weeks) with commercial diet without (C) or with 10% fructose in drinking water (F) alone or plus sitagliptin (CS and FS) or exendin-4 (CE and FE). Serum levels of metabolic/endocrine parameters, β-cell mass, morphology/ultrastructure and apoptosis, VMP1 expression and glucose-stimulated insulin secretion (GSIS) were studied. Complementary, islets isolated from normal rats were cultured (3 days) without (C) or with F and F plus exendin-4 (FE) or chloroquine (FCQ)...
February 10, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28188237/first-identification-of-kr%C3%A3-ppel-like-factor-2-mutation-in-heritable-pulmonary-arterial-hypertension
#20
Christina A Eichstaedt, Jie Song, Rebecca Rodríguez Viales, Zixuan Pan, Nicola Benjamin, Christine Fischer, Marius Hoeper, Silvia Ulrich, Katrin Hinderhofer, Ekkehard Grünig
Heritable pulmonary arterial hypertension (HPAH) is an autosomal dominantly inherited disease caused by mutations in the bone morphogenic protein receptor 2 gene and/or genes of its signalling pathway in about 85% of patients. We clinically and genetically analysed a HPAH family without mutations in previously described PAH genes. Clinical assessment included electrocardiogram, lung function, blood gas analysis, chest X-ray, laboratory testing, echocardiography and right heart catheterisation in case of suspected disease...
February 10, 2017: Clinical Science (1979-)
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