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Clinical Science (1979-)

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https://www.readbyqxmd.com/read/28341661/vascular-endothelial-growth-factor-a165b-ameliorates-outer-retinal-barrier-and-vascular-dysfunction-in-the-diabetic-retina
#1
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
#2
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
#3
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
#4
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
#5
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/28292971/selective-replacement-of-mitochondrial-dna-increases-cardioprotective-effect-of-chronic-continuous-hypoxia-in-spontaneously-hypertensive-rats
#6
Jan Neckar, Anna Svatonova, Romana Weissova, Zdenek Drahota, Pavlina Zajickova, Iveta Brabcova, David Kolar, Petra Alanova, Jana Vasinova, Jan Silhavy, Marketa Hlavackova, Katerina Tauchmannova, Marie Milerova, Bohuslav Ostadal, Ludek Cervenka, Jitka Zurmanova, Martin Kalous, Olga Novakova, Jiri Novotny, Michal Pravenec, Frantisek Kolar
Mitochondria play an essential role in improved cardiac ischemic tolerance conferred by adaptation to chronic hypoxia. In the present study, we analyzed effects of continuous normobaric hypoxia (CNH) on mitochondrial functions, including the sensitivity of mitochondrial permeability transition pore (MPTP) to opening, and infarct size in hearts of spontaneously hypertensive rats (SHR) and in conplastic SHR-mtBN strain characterized by the selective replacement of the mitochondrial genome of SHR with that of more ischemia-resistant Brown Norway (BN) strain...
March 14, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28289073/sympathetic-nervous-activity-in-patients-with-acute-coronary-syndrome-a-comparative-study-of-inflammatory-biomarkers
#7
Humberto Graner Moreira, Rony Lopes Lage, Daniel G Martinez, Larissa Ferreira-Santos, Maria U P B Rondon, Carlos Eduardo Negrão, Jose C Nicolau
Previous studies have shown that both sympathetic hyperactivity and enhanced inflammatory responses are associated with poor outcomes in patients with acute coronary syndrome (ACS). Whether there is a correlation between these two characteristics remains unclear. Thirty-four patients with uncomplicated ACS were evaluated; their mean age was 51.7 ± 7.0 years, 79.4% were male, and 94.1% had myocardial infarction. On the fourth day of hospitalization, they underwent muscle sympathetic nerve activity (MSNA) analysis (microneurography), as well as ultrasensitive C-reactive protein (usCRP), interleukin-6 (IL-6) and lipoprotein-associated phospholipase A2 (Lp-PLA2) activity measurements...
March 13, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28289072/downregulation-of-mir-15a-b-accelerates-fibrotic-remodelling-in-the-type-2-diabetic-human-and-mouse-heart
#8
Shruti Rawal, Pujika Emani Munasinghe, Prashanth Thevakar, Jason Kar Sheng Lew, Gregory T Jones, Michael Ja Willams, Philip Davis, Richard W Bunton, Ivor F Galvin, Patrick Manning, Regis R Lamberts, Rajesh G Katare
AIM: Myocardial fibrosis is a well established cause of increased myocardial stiffness and subsequent diastolic dysfunction in the diabetic heart. The molecular regulators that drive the process of fibrotic events in the diabetic heart are still unknown. We determined the role of the microRNA (miR)-15 family in fibrotic remodelling of the diabetic heart. METHODS AND RESULTS: Right atrial appendage (RAA) and left ventricular (LV) biopsy tissues collected from diabetic and non-diabetic patients undergoing coronary artery bypass graft surgery showed significant downregulation of miR-15a and -15b...
March 13, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28250083/synergistic-effects-of-citrulline-supplementation-and-exercise-on-performance-in-male-rats-evidences-for-implication-of%C3%A2-protein-and-energy-metabolisms
#9
Arthur Goron, Frédéric Lamarche, Valérie Cunin, Hervé Dubouchaud, Christophe Hourdé, Philippe Noirez, Christelle Corne, Karine Couturier, Michel Sève, Eric Fontaine, Christophe Moinard
Background: Exercise and citrulline are both regulators of muscle protein metabolism. However, the combination of both has been under-studied yet may have synergistic effects on muscle metabolism and performance. Methods: Three-month-old healthy male rats were randomly assigned to be fed ad libitum for 4 weeks with either a citrulline-enriched diet (1g/kg/day) ( CIT ) or an isonitrogenous standard diet (by addition of nonessential amino acid) ( Ctrl ) and trained (running on treadmill 5d/wk) ( ex ) or not. Maximal endurance activity and body composition were assessed, and muscle protein metabolism (protein synthesis, proteomic approach) and energy metabolism (energy expenditure, mitochondrial metabolism) were explored...
March 1, 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
#10
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
#11
Xiaofeng Tian, Dongcheng Feng, Jihong Yao, Guangzhi Wang, Zhenlu Li, Guo Zu, Yang Li, Fuwen Luo, Shili Ning, Wasim Qasim, Zhao Chen
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/28209631/hdpscs-fabricate-a-vascularised-woven-bone-tissue-a-new-tool-in-bone-tissue-engineering
#12
Francesca Paino, Marcella La Noce, Alessandra Giuliani, Alfredo De Rosa, Serena Mazzoni, Luigi Laino, Evzen Amler, Gianpaolo Papaccio, Vincenzo Desiderio, Virginia Tirino
Human dental pulp stem cells (hDPSCs) are mesenchymal stem cells successfully used in human bone tissue engineering. To better establish if these cells can lead to a bone tissue ready to be grafted, we checked DPSCs for their osteogenic and angiogenic differentiation capabilities with the specific aim to obtain a new tool for bone transplantation. Therefore, hDPSCs were specifically selected from the stromal-vascular dental pulp fraction, using appropriate markers and cultured. Growth curves, expression of bone-related markers, calcification, angiogenesis as well as in vivo transplantation assay were performed...
February 16, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28202686/simvastatin-pre-treatment-improves-survival-and-mitochondrial-function-in-a-three-day-fluid-resuscitated-rat-model-of-sepsis
#13
Jerome Morel, Iain Hargreaves, David Brealey, Viruna Neergheen, Janne T Backman, Sandro Lindig, Marcus Bläss, Michael Bauer, Daniel F McAuley, Mervyn Singer
Statins may offer protective effects in sepsis through anti-inflammatory, mitochondrial protection and other actions. We thus evaluated the effects of simvastatin on survival, organ and mitochondrial function, tissue and plasma ubiquinone levels and liver transcriptomics in a 3-day rat model of sepsis. Comparisons of rat plasma simvastatin and ubiquinone levels were made against levels sampled in blood from patients with acute lung injury (ALI) enrolled into a trial of statin therapy. Animals received simvastatin by gavage either pre- or post-induction of faecal peritonitis...
February 15, 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
#14
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
#15
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
#16
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
#17
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-)
https://www.readbyqxmd.com/read/28183811/annexin-ii-binding-immunoglobulins-in-patients-with-lupus-nephritis-and-their-correlation-with-disease-manifestations
#18
Kwok Fan Cheung, Susan Yung, Mel Km Chau, Desmond Yh Yap, Kwok Wah Chan, Cheuk Kwong Lee, Colin So Tang, Tak Mao Chan
Annexin II on mesangial cell surface mediates the binding of anti-dsDNA antibodies and consequent downstream inflammatory and fibrotic processes. We investigated the clinical relevance of circulating annexin II-binding immunoglobulins in patients with severe proliferative lupus nephritis, and renal annexin II expression in relation to progression of nephritis in NZBWF1/J mice. Annexin II-binding immunoglobulins in serum were measured by ELISA. Ultrastructural localization of annexin II was determined by electron microscopy...
February 9, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28143892/activation-of-trpv4-by-dietary-apigenin-antagonizes-renal-fibrosis-in-deoxycorticosterone-acetate-doca-salt-induced-hypertension
#19
Xing Wei, Peng Gao, Yunfei Pu, Qiang Li, Tao Yang, Hexuan Zhang, Shiqiang Xiong, Yuanting Cui, Li Li, Xin Ma, Daoyan Liu, Zhiming Zhu
Hypertension-induced renal fibrosis contributes to the progression of chronic kidney disease, and apigenin, an anti-hypertensive flavone that is abundant in celery, acts as an agonist of transient receptor potential vanilloid 4 (TRPV4). However, whether apigenin reduces hypertension-induced renal fibrosis, as well as the underlying mechanism, remain elusive. In this study, the deoxycorticosterone acetate (DOCA)-salt hypertension model was established in male Sprague-Dawley rats that were treated with apigenin or vehicle for 4 weeks...
January 31, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28143891/genome-wide-methylation-profiles-in-coronary-artery-ectasia
#20
Tzu-Pin Lu, Nai-Chen Chuang, Chin-Yu Cheng, Cheng-An Hsu, Yi-Chih Wang, Yen-Hong Lin, Jen-Kuang Lee, Cho-Kai Wu, Juey-Jen Hwang, Lian-Yu Lin, Shih-Fan Sherri Yeh, Kuo-Liang Chien, Jyh-Ming Jimmy Juang
Coronary artery ectasia (CAE) is a disease characterized by abnormally dilated coronary arteries. The mechanism of CAE remains unclear, and its treatment is limited. Previous studies showed that risk factors for CAE are related to changes in DNA methylation. However, no systematic investigation of methylation profiles has been performed. Therefore, we compared methylation profiles between 12 CAE patients and 12 propensity-matched individuals with normal coronary arteries using microarrays (Illumina HumanMethylation450)...
January 31, 2017: Clinical Science (1979-)
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