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Clinical Science (1979-)

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https://www.readbyqxmd.com/read/29773671/targeted-inhibition-of-cd74-attenuates-adipose-cox-2-mif-mediated-m1-macrophage-polarization-and-retards-obesity-related-adipose-tissue-inflammation-and-insulin-resistance
#1
Pei-Chi Chan, Ting-Ni Wu, Ying-Chuan Chen, Chieh-Hua Lu, Martin Wabitsch, Yu-Feng Tian, Po-Shiuan Hsieh
Adipose tissue (AT) inflammation is crucial to the development of obesity-associated insulin resistance. Our aim was to investigate the contribution of COX-2/MIF-mediated crosstalk between hypertrophic adipocytes and macrophages to the etiology of AT inflammation and involvement of CD74 using human SGBS adipocytes, THP-1 macrophages and mice fed a high-fat (HF) diet. The MIF and CD74 mRNA levels in the adipocytes and SVCs (stromal vascular cells) of white fat were highly correlated with body weight, HOMA-IR and adipose macrophage marker expression levels, especially those in SVCs...
May 17, 2018: Clinical Science (1979-)
https://www.readbyqxmd.com/read/29773670/high-%C3%AE-tocopherol-dosing-increases-lipid-metabolism-by-changing-redox-state-in-damaged-rat-gastric-mucosa-and-liver-after-ethanol-treatment
#2
Marisela Olguín-Martínez, Diego R Hernández-Espinosa, Rolando Hernández-Muñoz
Regeneration of ethanol-injured rat gastric mucosa must undergo changes in major metabolic pathways to achieve DNA replication and cell proliferation. These events are highly dependent on glucose utilization and inhibited by vitamin E (α-tocopherol) administration. Therefore, this study was aimed at assessing lipid metabolism in the gastric mucosa and ethanol-induced gastric damage and the effect of α-tocopherol administration. For this, rates of fatty acid β-oxidation and lipogenesis were tested in gastric mucosa samples...
May 17, 2018: Clinical Science (1979-)
https://www.readbyqxmd.com/read/29760122/perturbations-in-mitochondrial-dynamics-by-p66shc-lead-to-renal-tubular-oxidative-injury-in-human-diabetic-nephropathy
#3
Ming Zhan, Irtaza Usman, Jingbo Yu, Liemin Ruan, Xueyan Bian, Jun Yang, Shikun Yang, Lin Sun, Yashpal S Kanwar
Renal tubular injury is increasingly being recognized as an early characteristic of diabetic nephropathy (DN). Mitochondrial dynamic alterations and redox protein p66Shc-mediated oxidative stress are both critical for ensuing diabetic tubular cell injury and apoptosis; whether these two processes are interlinked remains unclear. In this study, we observed changes in mitochondrial morphology and expression of associated proteins in tubules of patients with DN. We demonstrated mitochondrial fragmentation as an important pathogenic feature of tubular cell injury that is linked to oxidative stress and p66Shc up-regulation...
May 14, 2018: Clinical Science (1979-)
https://www.readbyqxmd.com/read/29739827/hyperfiltration-in-ubiquitin-c-terminal-hydrolase-l1-deleted-mice
#4
Naomi C Boisvert, Chet E Holterman, Jean-François Thibodeau, Rania Nasrallah, Eldjonai Kamto, Cesar H Comin, Luciano da F Costa, Anthony Carter, Richard L Hébert, Alexey Gutsol, Gregory O Cron, Baptiste Lacoste, Douglas A Gray, Chris R Kennedy
Neuronal ubiquitin C-terminal hydrolase L1 (UCHL1) is a deubiquitinating enzyme that maintains intracellular ubiquitin pools and promotes axonal transport. Uchl1 deletion in mice leads to progressive axonal degeneration, affecting the dorsal root ganglion that harbours axons emanating to the kidney. Innervation is a crucial regulator of renal hemodynamics, though the contribution of neuronal UCHL1 to this is unclear. Immunofluorescence revealed significant neuronal UCHL1 expression in mouse kidney, including periglomerular axons...
May 8, 2018: Clinical Science (1979-)
https://www.readbyqxmd.com/read/29724769/pcsk9-inhibition-with-alirocumab-reduces-lipoprotein-a-levels-in-non-human-primates-by-lowering-apolipoprotein-a-production-rate
#5
Mikaël Croyal, Thi-Tu-Trang Tran, Rose Hélène Blanchard, Jean-Christophe Lebail, Elise F Villard, Bruno Poirier, Audrey Aguesse, Stéphanie Billon-Crossouard, Stéphane Ramin-Mangata, Valentin Blanchard, Brice Nativel, Kévin Chemello, Ilya Khantalin, Aurélie Thedrez, Philip Janiak, Michel Krempf, Christophe Boixel, Gilles Lambert, Etienne Guillot
Therapeutic antibodies targeting PCSK9 (e.g. alirocumab) lower low-density lipoprotein cholesterol (LDL-C) and lipoprotein (a) [Lp(a)] levels in clinical trials. We recently showed that PCSK9 enhances apolipoprotein(a) [apo(a)] secretion from primary human hepatocytes but does not affect Lp(a) cellular uptake. Here we aimed to determine how PCSK9 neutralization modulates Lp(a) levels in vivo. Six non-human primates (NHP) were treated with alirocumab or a control antibody (IgG1) in a crossover protocol. After the lowering of lipids reached steady state, NHP received an intravenous injection of [2H3]-leucine, and blood samples were collected sequentially over 48 hours...
May 3, 2018: Clinical Science (1979-)
https://www.readbyqxmd.com/read/29720422/gremlin-activates-the-notch-pathway-linked-to-renal-inflammation
#6
Carolina Lavoz, Jonay Poveda, Laura Márquez-Expósito, Sandra Rayego-Mateos, Raul R Rodrigues-Diez, Alberto Ortiz, Jesús Egido, Sergio Mezzano, Marta Ruiz-Ortega
Preclinical studies suggest that Gremlin participates in renal damage and could be a potential therapeutic target for human chronic kidney diseases. Inflammation is a common characteristic of progressive renal disease, and therefore novel anti-inflammatory therapeutic targets should be investigated. The Notch signaling pathway is involved in kidney development and is activated in human chronic kidney disease, but whether Gremlin regulates the Notch pathway has not been investigated. In cultured tubular cells, Gremlin up-regulated gene expression of several Notch pathway components, increased the production of the canonical ligand Jagged-1 and caused the nuclear translocation of active Notch-1 (N1ICD)...
May 2, 2018: Clinical Science (1979-)
https://www.readbyqxmd.com/read/29695588/mindin-deficiency-in-macrophages-protects-against-foam-cell-formation-and-atherosclerosis-by-targeting-lxr-%C3%AE
#7
Cheng Zhang, Juan-Juan Qin, Fu-Han Gong, Jing-Jing Tong, Wen-Lin Cheng, Haiping Wang, Yan Zhang, Xueyong Zhu, Zhi-Gang She, Hao Xia, Li-Hua Zhu
Abstract Background - Mindin, which is a highly conserved ECM protein, has been documented to play pivotal roles in regulating angiogenesis, inflammatory processes and immune responses. The aim of this study was to assess whether mindin contributes to the development of atherosclerosis. Methods and Results - A significant upregulation of Mindin expression was observed in the serum, arteries and atheromatous plaques of ApoE-/-  mice after HFD treatment. Mindin-/- ApoE-/- mice and macrophage-specific mindin overexpression in ApoE-/- mice (Lyz2-mindin-TG) were generated to evaluate the effect of mindin on the development of atherosclerosis...
April 25, 2018: Clinical Science (1979-)
https://www.readbyqxmd.com/read/29685981/angiotensin-1-7-reduces-cardiac-effects-of-thyroid-hormone-by-gsk3%C3%AE-nfatc3-signaling-pathway
#8
Nathalia Senger, Marcos Barrouin Melo, Gabriela Placoná Diniz, Maria José Campagnole-Santos, Robson Augusto Souza Dos Santos, Maria Luiza M Barreto-Chaves
Patients with hyperthyroidism exhibit increased risk of development and progression of cardiac diseases. The activation of the Renin Angiotensin System (RAS) has been indirectly implicated in these cardiac effects observed in hyperthyroidism. Angiotensin-(1-7) (Ang-(1-7)) has previously been shown to counterbalance pathological effects of Angiotensin II (Ang II). The aim of this study was to investigate the effects of elevated circulating Ang-(1-7) levels on cardiac effects promoted by hyperthyroidism in a transgenic rat (TG) model that constitutively overexpress an Ang-(1-7)-producing fusion protein [TGR(A1-7)3292]...
April 23, 2018: Clinical Science (1979-)
https://www.readbyqxmd.com/read/29674526/galectin-3-downregulates-antioxidant-peroxiredoxin-4-in-human-cardiac-fibroblasts-a-new-pathway-to-induce-cardiac-damage
#9
Jaime Ibarrola, Vanessa Arrieta, Rafael Sádaba, Ernesto Martínez-Martínez, Amaia García-Peña, Virginia Alvarez, Amaya Fernández-Celis, Alicia Gainza, Enrique Santamaría, Joaquin Fernández-Irigoyen, Victoria Cachofeiro, Guillermo Zalba, Renaud Fay, Patrick Rossignol, Natalia López-Andrés
Galectin-3 (Gal-3) is increased in heart failure (HF) and promotes cardiac fibrosis and inflammation. We investigated whether Gal-3 modulates oxidative stress in human cardiac fibroblasts, in experimental animal models and in human aortic stenosis (AS). Using proteomics and immunodetection approaches, we have identified that Gal-3 down-regulated the anti-oxidant peroxiredoxin-4 (Prx-4) in cardiac fibroblasts. In parallel, Gal-3 increased peroxide, nitrotyrosine, malondialdehyde and N-carboxymethyl-lysine levels and decreased total antioxidant capacity...
April 19, 2018: Clinical Science (1979-)
https://www.readbyqxmd.com/read/29650676/sodium-bicarbonate-loading-limits-tubular-cast-formation-independent-of-glomerular-injury-and-proteinuria-in-dahl-salt-sensitive-rats
#10
S C Ray, B Patel, D L Irsik, J Sun, H Ocasio, G R Crislip, C H Jin, J K Chen, B Baban, A J Polichnowski, P M O'Connor
Sodium bicarbonate (NaHCO3 ) slows the decline in kidney function in patients with chronic kidney disease (CKD), yet the mechanisms mediating this effect remain unclear. The Dahl salt-sensitive (SS) rat develops hypertension and progressive renal injury when fed a high salt diet; however, the effect of alkali loading on kidney injury has never been investigated in this model. We hypothesized that 'NaHCO3 protects from the development of renal injury in Dahl salt-sensitive rats via luminal alkalization which limits the formation of tubular casts, which are a prominent pathological feature in this model...
April 12, 2018: Clinical Science (1979-)
https://www.readbyqxmd.com/read/29632138/effects-of-dietary-salt-on-gene-and-protein-expression-in-brain-tissue-of-a-model-of-sporadic-small-vessel-disease
#11
Emma L Bailey, Martin W McBride, John D McClure, Wendy Beattie, Delyth Graham, Anna F Dominiczak, Colin Smith, Joanna M Wardlaw
Background: The effect of salt on cerebral small vessel disease (SVD) is poorly understood. We assessed the effect of dietary salt on the cerebral tissue of the stroke-prone spontaneously hypertensive rat (SHRSP) - a relevant model of sporadic SVD - at both the gene and protein level. Methods: Brains from 21 week old SHRSP and Wistar-Kyoto rats, half additionally salt-loaded (via a 3 week regime of 1% NaCl in drinking water) were split into 2 hemispheres and sectioned coronally - one hemisphere for mRNA microarray and qRT-PCR, the other for immunohistochemistry using a panel of antibodies targeting components of the neurovascular unit...
April 9, 2018: Clinical Science (1979-)
https://www.readbyqxmd.com/read/29626110/impaired-endocrine-metabolic-homeostasis-underlying-mechanism-of-its-induction-by-unbalanced-diet
#12
Bárbara Maiztegui, Carolina Lisi Román, Juan José Gagliardino, Luis Emilio Flores
Aim : to characterize the intrinsic mechanism by which sucrose induces β-cell dysfunction. Methods : Normal rats received for 3 weeks a standard diet supplemented with 10% sucrose in the drinking water (HS) with/out an antioxidant agent (R/S α-lipoic acid). We measured plasma glucose, insulin, triglyceride, leptin and lipid peroxidation levels; homeostasis model assessment-insulin resistance (HOMA-IR) and HOMA-β indexes were also determined. Insulin secretion, β-cell apoptosis, intracellular insulin and leptin mediators, and oxidative stress (OS) markers were also measured in islets isolated from each experimental group...
April 6, 2018: Clinical Science (1979-)
https://www.readbyqxmd.com/read/29581249/hypoxia-inducible-factor-prolyl-hydroxylase-inhibitor-roxadustat-fg-4592-protects-against-cisplatin-induced-acute-kidney-injury
#13
Yunwen Yang, Xiaowen Yu, Yue Zhang, Guixia Ding, Chunhua Zhu, Songming Huang, Zhanjun Jia, Aihua Zhang
Renal hypoxia occurs in acute kidney injury (AKI) of various etiologies. Activation of hypoxia-inducible transcription factor (HIF) has been identified as an important mechanism of cellular adaptation to low oxygen. Preconditional HIF activation protects against AKI, suggesting a new approach in AKI treatment. HIF is degraded under normoxic conditions mediated by oxygen-dependent hydroxylation of specific prolyl residues of the regulative α-subunits by HIF prolyl hydroxylases (PHD). FG-4592 is a novel, orally active small-molecule HIF PHD inhibitor for the treatment of anemia in patients with CKD...
March 26, 2018: Clinical Science (1979-)
https://www.readbyqxmd.com/read/29572385/microrna-27-3p-regulates-tlr2-4-dependent-mouse-alveolar-macrophage-activation-by-targeting-ppar%C3%AE
#14
Dan Wang, Sirong He, Bicui Liu, Chuntao Liu
Activation of alveolar macrophages (AMs) and the release of cytokines play critical roles in the pathogenesis of chronic obstructive pulmonary disease (COPD). However, little is known about the mechanisms of AM activation. miRNAs have recently emerged as key regulators of inflammation and as mediators of macrophage activation and polarization. We identified potential miRNAs related to AM activation using miRNA microarray analysis, which showed that miR-27-3p expression was up-regulated in AMs and the lung tissues of mice exposed to cigarette smoke (CS)/ lipopolysaccharide (LPS), and found that miR-27-3p regulated proinflammatory cytokine production and AM polarization depending on TLR2/4 intracellular signaling in AMs...
March 23, 2018: Clinical Science (1979-)
https://www.readbyqxmd.com/read/29572384/cardiotrophin-1-attenuates-experimental-colitis-in-mice
#15
Vanessa Prieto-Vicente, Ana I Sánchez-Garrido, Víctor Blanco-Gozalo, Miguel Arévalo, Enrique M García-Sánchez, Daniel López-Montañés, Yaremi Quirós, Francisco J López-Hernández, Antonio Rodríguez-Pérez, José M López-Novoa
Cardiotrophin-1 (CT-1) holds potent anti-inflammatory, cytoprotective and anti-apoptotic effects in the liver, kidneys and heart. In this study the role of endogenous CT-1 and the effect of exogenous CT-1 were evaluated in experimental ulcerative colitis. Colitis was induced in CT-1 knock-out and wild type mice by administration of dextran sodium sulphate (DSS) in the drinking water during 7 days. CT-1 knock-out mice showed higher colon damage and disease severity than wild type mice. In addition, CT-1 (200 µg/kg/day, iv) or vehicle (as control) were administered during 3 days to wild type, colitic mice, starting on day 4 after initiation of DSS...
March 23, 2018: Clinical Science (1979-)
https://www.readbyqxmd.com/read/29572383/ctrp3-attenuates-high-fat-diet-induced-male-reproductive-dysfunction-in-mice
#16
Yang Mu, Tai-Lang Yin, Lu Yin, Xue Hu, Jing Yang
Recent studies have suggested a role for abdominal obesity in male infertility. Previous studies have found that cell apoptosis exerts an important role in obesity-related male infertility. C1q/TNF-related protein 3 (CTRP3), a paralog of adiponectin, has been proposed to exert anti-apoptotic effects and to attenuate diabetes-related cardiac injuries. However, the role of CTRP3 in high-fat diet (HFD)-induced spermatogenic impairment remains unclear. In the present study, we fed male mice a HFD for 24 weeks to induce obesity...
March 23, 2018: Clinical Science (1979-)
https://www.readbyqxmd.com/read/29540539/identification-of-protein-phosphatase-involvement-in-the-at-2-receptor-induced-activation-of-endothelial-nitric-oxide-synthase
#17
A Augusto Peluso, Jesper Bork Bertelsen, Kenneth Andersen, Tenna Pavia Mortensen, Pernille B Hansen, Colin Sumners, Michael Bader, Robson A Santos, U Muscha Steckelings
The angiotensin AT2 receptor (AT2 R) promotes vasodilation by nitric oxide (NO) release from endothelial cells. However, the mechanisms underlying the AT2 R-induced stimulation of endothelial NO synthase (eNOS) is still not completely understood. Therefore, we investigated whether in addition to the known AT2 R-mediated phosphorylation of eNOS at Ser1177, activation of phosphatases and dephosphorylation of eNOS at Tyr657 and Thr495 are also involved. Human Aortic Endothelial Cells (HAEC) were stimulated with the AT2 R-agonist C21 (1µM) in the presence or absence of either PD123319 (10µM; AT2 R-antagonist), L-NAME (10µM; eNOS inhibitor), MK-2206 (100nM; Akt-inhibitor) sodium fluoride (1nM; serine/threonine-phosphatase inhibitor) or sodium orthovanadate (10nM; tyrosine-phosphatase inhibitor)...
March 14, 2018: Clinical Science (1979-)
https://www.readbyqxmd.com/read/29540538/a77-1726-leflunomide-blocks-and-reverses-cardiac-hypertrophy-and-fibrosis-in-mice
#18
Zhen-Guo Ma, Xin Zhang, Yu-Pei Yuan, Ya-Ge Jin, Ning Li, Chun-Yan Kong, Peng Song, Qi-Zhu Tang
T cell infiltration and the subsequently increased intracardial chronic inflammation play crucial roles in the development of cardiac hypertrophy and heart failure. A77 1726, the active metabolite of leflunomide, has been reported to have powerful anti-inflammatory and T cells-inhibiting properties. However, the effect of A77 1726 on cardiac hypertrophy remains completely unknown. Herein, we found that A77 1726 treatment attenuated pressure overload or angiotensin II-induced cardiac hypertrophy in vivo, as well as agonist-induced hypertrophic response of cardiomyocytes in vitro...
March 14, 2018: Clinical Science (1979-)
https://www.readbyqxmd.com/read/29540537/metformin-inhibits-inflammatory-signals-in-the-gut-by-controlling-ampk-and-p38-map-kinase-activation
#19
Davide Di Fusco, Vincenzo Dinallo, Ivan Monteleone, Federica Laudisi, Irene Marafini, Eleonora Franzè, Antonio Di Grazia, Rami Dwairi, Alfredo Colantoni, Angela Ortenzi, Carmine Stolfi, Giovanni Monteleone
Metformin, a hypoglycemic drug used for treatment of type 2 diabetes, regulates also inflammatory pathways. By using several models of intestinal inflammation, we examined whether metformin exerts anti-inflammatory effects and investigated the basic mechanism by which metformin blocks pathologic signals. Colitic mice given metformin exhibited less colonic inflammation and increased expression of active AMP-activated protein kinase, a mediator of the metabolic effects of metformin, in both epithelial and lamina propria compartments...
March 14, 2018: Clinical Science (1979-)
https://www.readbyqxmd.com/read/29535266/prader-willi-region-non-protein-coding-rna-1-suppressed-gastric-cancer-growth-as-a-competing-endogenous-rna-of-microrna-425-5p
#20
Zihao Chen, Hongping Ju, Shan Yu, Ting Zhao, Xiaojie Jing, Ping Li, Jing Jia, Nan Li, Bibo Tan, Yong Li
Gastric cancer (GC) is one of a major global health problem especially in Asia. Nowadays, long non-coding RNA has gained significantly attention in the current research climate such as carcinogenesis. This research desired to explore the mechanism of Prader-Willi region non-protein coding RNA 1 (PWRN1) on regulating GC process. Differentially expressed lncRNAs in GC tissues were screened out through microarray analysis. The RNA and protein expression level was detected by qRT-PCR and western blot. Cell proliferation, apoptosis rate, metastasis abilities were respectively determined by CCK8, flow cytometry, wound healing and transwell assay...
March 13, 2018: Clinical Science (1979-)
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