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Clinical Science (1979-)

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https://www.readbyqxmd.com/read/28687713/tlr9-is-upregulated-in-human-and-murine-nash-pivotal-role-for-inflammatory-recruitment-and-cell-survival
#1
Auvro R Mridha, Fahrettin Haczeyni, Matthew M Yeh, W Geoffrey Haigh, George N Ioannou, Vanessa Barn, Hussam Ajamieh, Leon Adams, Jeffrey M Hamdorf, Narci C Teoh, Geoffrey C Farrell
Background & Aims: TLR9 deletion protects against steatohepatitis due to choline-amino acid depletion and high-fat diet. We measured TLR9 in human NASH livers, and tested whether TLR9 mediates inflammatory recruitment in three murine models of NAFLD. Methods: We assayed TLR mRNA in liver biopsies from bariatric surgery patients. Wildtype (Wt) , appetite-dysregulated Alms1 mutant (foz/foz),Tlr9(-/-), and Tlr9(-/-).foz/foz C57BL6/J mice and bone marrow (BM) chimeras were fed 0.2% cholesterol, high-fat, high sucrose (atherogenic[Ath]) diet or chow, and NAFLD activity score (NAS)/NASH pathology, macrophage/neutrophil infiltration, cytokines/chemokines and cell death markers measured in livers...
July 7, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28667120/chronic-cerebral-hypoperfusion-alters-amyloid-%C3%AE-peptide-pools-leading-to-cerebral-amyloid-angiopathy-microinfarcts-and-hemorrhages-in-tg-swdi-mice
#2
Natalia Salvadores, James L Searcy, Philip R Holland, Karen Horsburgh
Cerebral hypoperfusion is an early feature of Alzheimer's disease (AD) that influences the progression from mild cognitive impairment to dementia. Understanding the mechanism is of critical importance in the search for new effective therapies. We hypothesised that cerebral hypoperfusion promotes the accumulation of amyloid-β (Ab) and degenerative changes in the brain and is a potential mechanism contributing to development of dementia. To address this we studied the effects of chronic cerebral hypoperfusion induced by bilateral carotid artery stenosis on Ab peptide pools in a transgenic mouse model of AD (Tg-SwDI) at an age when fibrillar amyloid burden is minimal...
June 30, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28646123/expression-of-mir-23a-induces-telomere-shorteningand-is-associated-with-poor-clinical-outcomesin-patients-with-coronary-artery-disease
#3
Mamoru Satoh, Takahito Nasu, Yuji Takahashi, Takuya Osaki, Sho Hitomi, Yoshihiro Morino, Motoyuki Nakamura
Telomeric repeat binding factor 2 (TRF2) plays an important role in telomere maintenance. MicroRNA (miR)-23a may directly inhibit TRF2 expression, inducing telomere shortening and cellular senescence. This study aimed to determine whether miR-23a and TRF2 are expressed in patients with coronary artery disease (CAD), and whether pitavastatin might affect these levels. This study included 104 patients with CAD and 50 controls. Patients with CAD were randomly divided into two subgroups [a moderate lipid lowering therapy (LLT) group and an aggressive LLT group]...
June 23, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28646122/nintedanib-a-triple-tyrosine-kinase-inhibitor-attenuates-renal-fibrosis-in-chronic-kidney-disease
#4
Feng Liu, Li Wang, Hualin Qi, Jun Wang, Wei Jiang, Yi Wang, Liuqing Xu, Na Liu, Shougang Zhuang
Nintedanib (BIBF1120) is a triple kinase inhibitor of platelet derived growth factor receptor (PDGFR), fibroblast growth factor receptors (FGFR), vascular endothelial growth factor receptor (VEGFR) and Src family kinase, that has recently been approved by FDA to treat idiopathic pulmonary fibrosis. Whether it affects renal fibrosis remains unknown. Here we demonstrated that administration of nintedanib immediately or 3 days after unilateral ureteral obstruction (UUO) injury and with folic acid injection attenuated renal fibrosis and inhibited activation of renal interstitial fibroblasts...
June 23, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28646121/at1-receptor-blockade-attenuates-outward-aortic-remodeling-associated-with-diet-induced-obesity-in-mice
#5
Friedrich Krueger, Kai Kappert, Anna Foryst-Ludwig, Frederike Kramer, Markus Clemenz, Aleksandra Grzesiak, Manuela Sommerfeld, Jan Paul Bernhard Frese, Andreas Greiner, Ulrich Kintscher, Thomas Unger, Elena Kaschina
The renin-angiotensin-system and obesity have been implicated in vascular outward remodeling, including aneurysms, but the precise mechanisms are yet not understood. We investigated the effect of the angiotensin AT1-receptor antagonist telmisartan on aortic outward remodeling in a diet-induced obesity-model in mice. C57/Black6J mice were fed with either a low-fat diet (LFD), or a high-fat diet (HFD) for 14 weeks. One group of HFD-mice was additionally exposed to telmisartan (3mg/kg/d) for the last 4 weeks. HFD led to aortic outward remodeling, characterized by increased proteolysis, along with structural changes, such as fragmentation of elastic fibres, and decreased elastin content...
June 23, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28646120/mir-223-represents-a-biomarker-in-acute-and-chronic-liver-injury
#6
Florian Schueller, Sanchari Roy, Sven Heiko Loosen, Jan Alder, Christiane Koppe, Anne Theres Schneider, Franziska Wandrer, Heike Bantel, Mihael Vucur, Qing-Sheng Mi, Christian Trautwein, Tom Luedde, Christoph Roderburg
Background: Dysregulation of miRNAs has been described in tissue and serum from patients with acute and chronic liver diseases. However, only little information on the role of miR-223 in the pathophysiology of acute liver failure (ALF) and liver cirrhosis is available.  Methods: We analysed cell and tissue specific expression levels as well as serum concentrations of miR-223 in mouse models of acute (hepatic ischemia and reperfusion, single CCl4 injection) and chronic (repetitive CCl4 injection, bile duct ligation) liver diseases...
June 23, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28642294/mhc-class-ii-invariant-chain-peptide-or-gamma-delta-t-cell-depletion-ameliorates-experimental-preeclampsia
#7
Piyali Chatterjee, Valorie L Chiasson, Geetha Seerangan, Eugene De Guzman, Moheb Milad, Kelsey R Bounds, Olga Gasheva, Richard P Tobin, Mohamad Hatahet, Shelley Kopriva, Kathleen A Jones, M Karen Newell-Rogers, Brett Mitchell
Excessive innate immune system activation and inflammation during pregnancy can lead to organ injury and dysfunction and preeclampsia; however, the molecular mechanisms involved are unknown.  We tested the hypothesis that Toll-like receptor activation induces MHC class II invariant chain peptide (CLIP) expression on immune cells, makes them pro-inflammatory, and are necessary to cause preeclampsia-like features in mice.  Treatment with VG1177, a competitive antagonist peptide for CLIP in the groove of MHC class II, was able to both prevent and treat preeclampsia-like features in mice...
June 22, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28634189/reduced-platelet-count-but-no-major-platelet-function-abnormalities-are-associated-with-loss-of-function-atp-binding-cassette-1-abca1-gene-mutations
#8
Pietro Minuz, Alessandra Meneguzzi, Eti Alessandra Femia, Cristiano Fava, Stefano Calabria, Mariangela Scavone, Donatella Benati, Giovanni Poli, Carlo Zancanaro, Sebastiano Calandra, Tiziano Lucchi, Marco Cattaneo
Loss of function mutations of the the ATP-binding cassette-1 (ABCA1) gene are the cause of Tangier disease (TD) in homozygous subjects and familial HDL deficiency (FHD) in heterozygous subjects. These disorders are characterized by reduced plasma HDL-cholesterol and altered efflux of cholesterol from cells. Previous studies in TD patients and ABCA1(-/-) murine models reported defects in platelet count, morphology and function, but the issue is still controversial. We analysed three subjects with low to very low HDL cholesterol levels due to loss of function mutations of the ABCA1 gene...
June 20, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28620012/metabolic-disturbances-of-non-alcoholic-fatty-liver-resemble-the-alterations-typical-for-type-2-diabetes
#9
Bram Brouwers, Vera B Schrauwen-Hinderling, Tomas Jelenik, Anne Gemmink, Bas Havekes, Yvonne Bruls, Dennis Dahlmans, Michael Roden, Matthijs K C Hesselink, Patrick Schrauwen
Non-alcoholic fatty liver (NAFL) is an independent risk factor for the development of type 2 diabetes (T2DM). We examined metabolic perturbations in people with NAFL, patients with T2DM and people with normal intrahepatic lipid (IHL) (CON). A 2-step (10mU/m(2)/min, 40mU/m(2)/min) hyperinsulinemic-euglycemic clamp was performed in 11 NAFL, 13 T2DM and 11 CON, all matched for BMI and aerobic fitness. IHL was measured using proton magnetic resonance spectroscopy. Because of high IHL variability in T2DM patients, this group was separated into a high IHL (IHL≥5...
June 15, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28611236/quantification-of-circulating-gdf-11-and-%C3%AE-2-mg-in-aged-patients-with-age-related-impairment-in-cognitive-function
#10
Rungong Yang, Shuhong Fu, Liang Zhao, Bei Zhen, Ling Ye, Xiaolu Niu, Xiaoxia Li, Pumin Zhang, Jie Bai
GDF-11 has been implicated in reverse effects of aging on the central nervous system of humans. β2-MG has been reported to negatively regulate cognitive. However, there is a lot of controversy about the role of GDF-11 and β2-MG in ageing and cognitive regulation. Objective: To examine the involvement of GDF-11 and β2-MG in the aging process and cognitive dysfunction. Methods: A total of 51 healthy subjects and 41 elderly patients with different degrees of age-related cognitive impairment participated in the study...
June 13, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28611235/improvement-in-exercise-duration-lung-function-and-well-being-in-g551d-cystic-fibrosis-patients-a-double-blind-placebo-controlled-randomised-cross-over-study-with-ivacaftor
#11
Dominic T Keating, Deirdre Edgeworth, Matthew Ellis, Brenda Button, Elyssa Williams, Denise Clark, Audrey Tierney, Stephane Heritier, Anastase T Kotsimbos, John Wilson
G551D , a mutation of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, results in impaired chloride channel function in cystic fibrosis (CF) with multiple end-organ manifestations. The effect of ivacaftor, a CFTR-potentiator, on exercise capacity in cystic fibrosis (CF) is unknown. Twenty G551D-CF patients were recruited to a single-centre, double-blind, placebo-controlled, 28-day crossover study of ivacaftor. Variables measured included percentage change from baseline (%Δ) of VO2max (maximal oxygen consumption, primary outcome) during cardiopulmonary exercise testing (CPET), relevant other CPET physiological variables, lung function, BMI, sweat chloride, and disease specific health related quality of life (QOL) measures (CFQ-R and Alfred Wellness (AWEscore))...
June 13, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28592554/urinary-glycated-uromodulin-in-diabetic-kidney-disease
#12
Chia-Chu Chang, Chen-Yu Chen, Ching-Hui Huang, Chia-Lin Wu, Hung-Ming Wu, Ping-Fang Chiu, Chew-Teng Kor, Ting-Huan Chen, Geen-Dong Chang, Cheng-Chin Kuo, Hui-Chin Wen, Chih-Yang Huang, Chung-Ho Chang
Advanced glycation end products (AGEs) form during oxidative stress, which is increased in diabetes mellitus (DM). Uromodulin is a protein with a renal protective effect, and may be subject to glycation. The implications of uromodulin glycation and AGEs in the urine are not understood. Here, immunoprecipitation and liquid chromatography-mass spectrometry identified glycated uromodulin (glcUMOD) in the urine of 62.5% of patients with diabetic kidney disease (DKD), 20.0% of patients with non-diabetic chronic kidney disease (CKD) but non-DM, and no DM patients with normal renal function or healthy control participants; a finding replicated in a larger cohort of 84 patients with CKD in a case-control study (35 with DM, 49 without)...
June 7, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28588103/mycobacteriumtuberculosis-rv3615c-is-a-highly-immunodominant-antigen-and-specifically-inducespotent-th1-type-immune-responses-in-tuberculosis-pleurisy
#13
Jiangping Li, Juan Shen, Suihua Lao, Xiaomin Li, Jie Liu, Changyou Wu
T-cell responses have been demonstrated essential for preventing M.tb infection. The Th1-cytokines produced by T cells, such as INF-γ, IL-2 and TNF-α, not only limit the invasion of M.tb but also eliminate the pathogen at site of infection. BCG is known to induce Th1-type responses but the protection is inadequate. Identification of immunogenic components in addition to those expressed in BCG and induction of a broad spectrum of Th1-type responses provide options for generating sufficient adaptive immunity...
June 6, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28572401/abcb1-gene-polymorphism-associated-with-clinical-factors-can-predict-drug-resistant-tuberculosis
#14
Yasmin Pontual, Vanessa da Silveira Dos Santos Pacheco, Sergio Pereira Monteiro, Marcel S B Quintana, Marli Jane Martins Costa, Valeria Cavalcanti Rolla, Liane De Castro
Polymorphism in ABCB1 gene encoding P-glycoprotein, a transmembrane drug efflux pump, contributes to drug resistance and have been widely studied, however, their association with rifampicin and ethambutol resistance in tuberculosis patients are still unclear. Genotype/allele/haplotype frequencies in c.1236C>T (rs1128503), c.2677G>T/A (rs2032582) and c.3435C>T (rs1045642) were obtained from 212 patients, of these, 80 patients with rifampicin and/or ethambutol resistance were selected as case group and 132 control-group through the result of their culture and drugs sensitive test...
June 1, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28566469/visceral-adipose-tissue-activated-macrophage-content-and-inflammatory-adipokine-secretion-is-higher-in-pre-eclampsia-than-in-healthy-pregnancy
#15
Shahzya Huda, FIona Jordan, JAck Bray, Gillian Love, Reba Payne, Naveed Sattar, Dilys J Freeman
Obesity increases preeclampsia risk. Adipose tissue inflammation may contribute to the clinical syndrome of pre-eclampsia. We compared adipose tissue macrophage infiltration and release of pro-inflammatory adipokines in pre-eclampsia and healthy pregnancy. Subcutaneous and visceral adipose tissue biopsies were collected from healthy (n=13) and preeclampsia (n=13) mothers. Basal and lipopolysaccharide stimulated adipocyte TNFα, IL-6, CCL-2 and CRP release was measured. Adipose tissue cell densities of activated (cfms(+)) and total (CD68(+)) macrophages were determined...
May 31, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28559425/fgf21-ameliorates-diabetic-cardiomyopathy-by-activating-the-ampk-paraoxonase-1-signaling-axis-in-mice
#16
Fan Wu, Baile Wang, Saisai Zhang, Lihua Shi, Yanfang Wang, Rongrong Xiong, Xuebo Pan, Fanghua Gong, Xiaokun Li, Zhuofeng Lin
Aims: The aim in present study is to explore the molecular mechanism of FGF21 against diabetic cardiomyopathy. Materials and methods: FGF21 deficient mice and wild type littermates were used to induce diabetic mice by treatment with streptozotocin/high-fat diet (STZ/HFD), and then evaluated the difference of diabetic cardiomyopathy between two types of mice. Otherwise, primary cultured cardiomyocytes were also used to explore the potential molecular mechanism of FGF21 against high glucose-induced cardiomyocyte injuries...
May 30, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28550144/exacerbation-of-oxygen-glucose-deprivation-induced-blood-brain-barrier-disruption-potential-pathogenic-role-of-interleukin-9-in-ischemic-stroke
#17
Sha Tan, Yilong Shan, Yuge Wang, Yinyao Lin, Siyuan Liao, Zhezhi Deng, Li Zhou, Wei Cai, Qin Zeng, Lei Zhang, Bingjun Zhang, Xuejiao Men, Haiyan Li, Xueqiang Hu, Changyou Wu, Lisheng Peng, Zhengqi Lu
Interleukin (IL) -9 exerts a variety of functions in autoimmune diseases. However, its role in ischemic brain injury remains unknown. The present study explored the biological effects of IL-9 in ischemic stroke. We recruited 42 patients newly diagnosed with ischemic stroke and 22 age- and sex-matched healthy controls. The expression levels of IL-9 and percentages of IL-9-producing T cells, including CD3+CD4+IL-9+ and CD3+CD8+IL-9+ cells, were determined in peripheral blood mononuclear cells (PBMCs) obtained from patients and control individuals...
May 26, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28539328/dynamic-response-toinitial-stage-blindnessin-visual-system-development
#18
Erping Long, Xiayin Zhang, Zhenzhen Liu, Xiaohang Wu, Xuhua Tan, Duoru Lin, Qianzhong Cao, Jingjing Chen, Zhuoling Lin, Dongni Wang, Xiaoyan Li, Jing Li, Jinghui Wang, Wangting Li, Haotian Lin, Weirong Chen, Yizhi Liu
Sensitive periods and experience-dependent plasticity have become core issues in visual system development. Converging evidence indicates that visual experience is an indispensable factor in establishing mature visual system circuitry during sensitive periods and the visual system exhibits substantial plasticity when facing deprivation. The mechanisms that underlie the environmental regulation of visual system development and plasticity are of great interest but need further exploration. Here, we investigated a unique sample of human infants who experienced initial stage blindness (beginning at birth and lasting 2 to 8 months) before the removal of bilateral cataracts...
May 24, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28536293/peroxisome-proliferator-activated-receptor-%C3%AE-agonism-attenuates-endotoxaemia-induced-muscle-protein-loss-and-lactate-accumulation-in%C3%A2-rats
#19
Hannah Crossland, Dumitru Constantin-Teodosiu, Sheila Gardiner, Paul Greenhaff
The peroxisome proliferator-activated receptor γ (PPARγ) agonist rosiglitazone (Rosi) appears to provide protection against organ dysfunction during endotoxaemia. We examined the potential benefits of Rosi on skeletal muscle protein maintenance and carbohydrate metabolism during lipopolysaccharide (LPS)-induced endotoxaemia. Sprague-Dawley rats were fed either standard chow (control) or standard chow containing Rosi (8.5±0.1 mg(.)kg(-1.)day(-1)) for two weeks before and during 24 h continuous intravenous infusion of LPS (15 μg(...
May 23, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28533215/inhibition-of-hdac3-prevents-diabetic-cardiomyopathy-in-ove26-mice-via-epigenetic-regulation-of-dusp5-erk1-2-pathway
#20
Zheng Xu, Qian Tong, Zhiguo Zhang, Shudong Wang, Yang Zheng, Qiuju Liu, Lingbo Qian, Shao-Yu Chen, Jian Sun, Lu Cai
Inhibition of total histone deacetylases (HDACs) was phenomenally associated with the prevention of diabetic cardiomyopathy (DCM). However, which specific HDAC plays the key role in DCM remains unclear. The present study was designed to determine whether DCM can be prevented by specific inhibition of HDAC3 and to elucidate the mechanisms by which inhibition of HDAC3 prevent DCM. Type 1 diabetes OVE26 and age-matched wild-type mice were given the selective HDAC3 inhibitor RGFP966 or vehicle for 3 months. These mice were then sacrificed immediately or 3 months later for cardiac function and pathological examination...
May 22, 2017: Clinical Science (1979-)
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