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https://www.readbyqxmd.com/read/29774570/high-mobility-group-box-1-drives-fibrosis-progression-signaling-via-the-receptor-for-advanced-glycation-end-products-in-mice
#1
Xiaodong Ge, Elena Arriazu, Fernando Magdaleno, Daniel J Antoine, Rouchelle Dela Cruz, Neil Theise, Natalia Nieto
BACKGROUND & RATIONALE: High-mobility group box-1 (HMGB1) is a damage-associated molecular pattern (DAMP) increased in response to liver injury. Since HMGB1 is a ligand for the receptor for advanced glycation end-products (RAGE), we hypothesized that induction of HMGB1 could participate in the pathogenesis of liver fibrosis via RAGE cell-specific signaling mechanisms. RESULTS: liver HMGB1 protein expression correlated with fibrosis stage in patients with chronic Hepatitis C virus (HCV) infection, primary biliary cirrhosis (PBC) and alcoholic steatohepatitis (ASH)...
May 18, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29763344/from-the-valley-of-death-to-the-crossroads-of-opportunity-a-discussion-of-evolving-benefit-risk-evaluation-standards
#2
Peter J Pitts, Patrick Brady
A series of recent US Food and Drug Administration (FDA) approvals (such as Sarepta's Exondys 51, Merck's Keytruda, and Portola's Bevyxxa) has generated significant interest within the drug development ecosystem. Facilitated regulatory pathways aimed toward expediting medicines to patients suffering from serious and life-threatening conditions are a good thing, even if it raises curiosity and introduces some degree of uncertainty. Over the last 20 years, two key words in drug development have been speed and innovation...
January 1, 2018: Therapeutic Innovation & Regulatory Science
https://www.readbyqxmd.com/read/29758944/the-conundrum-of-gsk3-inhibitors-is-it-the-dawn-of-a-new-beginning
#3
Ratan V Bhat, Ulf Andersson, Shalini Andersson, Laurent Knerr, Udo Bauer, Anna Sundgren Andersson
Spanning over three decades of extensive drug discovery research, the efforts to develop a potent and selective GSK3 inhibitor as a therapeutic for the treatment of type 2 diabetes, Alzheimer's disease (AD), bipolar disorders and cancer have been futile. Since its initial discovery in 1980 and subsequent decades of research, one cannot underscore the importance of the target and the promise of a game changing disease modifier. Several pharmaceutical companies, biotech companies, and academic institutions raged in a quest to unravel the biology and discover potent and selective GSK3 inhibitors, some of which went through clinical trials...
May 11, 2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29754053/novel-electrochemical-sensing-platform-for-ultrasensitive-detection-of-cardiac-troponin-i-based-on-aptamer-mos-2-nanoconjugates
#4
Xiujuan Qiao, Kunxia Li, Jinqiong Xu, Ni Cheng, Qinglin Sheng, Wei Cao, Tianli Yue, Jianbin Zheng
Cardiac troponin I (cTnI) is a specific and sensitive biomarker for the early diagnosis of acute myocardial infarction and for the subsequent clinical treatments. In this work, novel electrochemical sensing platform for sensing of cTnI based on aptamer-MoS2 nanoconjugates was proposed. For comparison, core-shell Au@SiO2 @Au nanoparticles were also used for sensing of cTnI. The sensing schemes and electrochemical responses of the proposed sensors were investigated by electrochemical impedance spectroscopy (EIS) in 5...
May 4, 2018: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/29753380/chronic-alcohol-ingestion-impairs-rat-alveolar-macrophage-phagocytosis-via-disruption-of-rage-signaling
#5
Bashar S Staitieh, Eduardo E Egea, Xian Fan, Adaugo Amah, David M Guidot
BACKGROUND: Alcohol significantly impairs antioxidant defenses and innate immune function in the lung and increases matrix metalloproteinase 9 (MMP-9) activity. The receptor for advanced glycation end products (RAGE) is a well-characterized marker of lung injury that is cleaved by MMP-9 into soluble RAGE and has not yet been examined in the alcoholic lung. We hypothesized that chronic alcohol ingestion would impair RAGE signaling via MMP-9 in the alveolar macrophage and thereby impair innate immune function...
May 2018: American Journal of the Medical Sciences
https://www.readbyqxmd.com/read/29750887/the-effects-of-acute-hypoxia-on-tissue-oxygenation-and-circulating-alarmins-in-healthy-adults
#6
C J Boos, C M Lamb, M Midwinter, A Mellor, D R Woods, M Howley, T Stansfield, M Foster, J P O'hara
The binding of high-mobility group box-1 (HMGB-1) to the membrane receptor for advanced glycation end-products (mRAGE) is a key early mediator of non-infectious inflammation and its triggers include ischaemia/hypoxia. The effects of acute hypoxia on soluble RAGE (sRAGE) are unknown. Fourteen healthy adults (50% women; 26.6+/-3.8 years) were assessed at baseline normoxia (T0), followed by four time-points (T90, 95, 100 and 180 minutes) over three hours of continuous normobaric hypoxia (NH, 4450m equivalent) and again 60 minutes after return to normoxia (T240)...
May 10, 2018: Physiological Research
https://www.readbyqxmd.com/read/29747745/the-potential-effect-of-garlic-extract-and-curcumin-nanoparticles-against-complication-accompanied-with-experimentally-induced-diabetes-in-rats
#7
Afaf D Abdel-Mageid, Mohamed E S Abou-Salem, Nancy M H A Salaam, Hoda A S El-Garhy
BACKGROUND: Modified herbal medicines implicate the combination of several therapeutic practices of native systems of medicine that may extend many earlier generations, which frequently afford valuable therapeutic benefits. PURPOSE: In this study, the role of nano-curcumin and aged garlic extract (AGE) as two modified phytomedicines on alleviating both of advanced glycation end products (AGEPs) and oxidative stress (OS) in streptozotocin (STZ) induced diabetic rats were investigated during this study...
April 1, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/29746703/s100a8-a9-promotes-parenchymal-damage-and-renal-fibrosis-in-obstructive-nephropathy
#8
Alessandra Tammaro, Sandrine Florquin, Mascha Brok, Nike Claessen, Loes M Butter, Gwendoline J D Teske, Onno J de Boer, Thomas Vogl, Jaklien C Leemans, Mark C Dessing
Despite advances in our understanding of the mechanisms underlying progression of chronic kidney disease and the development of fibrosis, only limited efficacious therapies exist. The calcium binding protein S100A8/A9, is a damage-associated molecular pattern which can activate TLR4 or RAGE. Activation of these receptors is involved in the progression of renal fibrosis, however the role of S100A8/A9 herein remains unknown. Therefore, we analyzed S100A8/A9 expression in patients and mice with obstructive nephropathy and subjected wild-type and S100A9 KO mice lacking the heterodimer S100A8/A9 to Unilateral Ureteral Obstruction (UUO)...
May 10, 2018: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/29744367/age-rage-induced-emp-release-via-the-nox-derived-ros-pathway
#9
Ying-Hua Chen, Zhang-Wei Chen, Hong-Mei Li, Xin-Feng Yan, Bo Feng
Objective: Diabetes is associated with accelerated formation of advanced glycation end products (AGEs) that are extensively found in circulating endothelial microparticles (EMPs). This study aimed to investigate whether AGEs have a direct effect on EMP formation and the possible underlying mechanism. Methods: In vitro, cultured human umbilical vein endothelial cells (HUVECs) were incubated with AGEs (200 and 400  μ g/ml) for 24 hours with or without pretreatment with anti-RAGE antibody, NOX inhibitor, or ROS scavenger...
2018: Journal of Diabetes Research
https://www.readbyqxmd.com/read/29737911/immunolocalization-of-advanced-glycation-end-products-mitogen-activated-protein-kinases-and-transforming-growth-factor-%C3%AE-smads-in-pelvic-organ-prolapse
#10
Antonella Vetuschi, Simona Pompili, Anna Gallone, Angela D'Alfonso, Maria Gabriella Carbone, Gaspare Carta, Claudio Festuccia, Eugenio Gaudio, Alessandro Colapietro, Roberta Sferra
Collagen and matrix metalloproteinases (MMP) play a pivotal role in the pathophysiology of Pelvic Organ Prolapse (POP) as a switch between type I and III collagen together with a simultaneous activation of MMPs have been observed in the vaginal wall. The aim of this study was to evaluate the Advanced Glycation End (AGE) products, ERK1/2 and transforming growth factor (TGF)-β/Smad pathway expression in muscularis propria in women with POP compared with control patients. We examined 20 patients with POP and 10 control patients treated for uterine fibromatosis...
May 1, 2018: Journal of Histochemistry and Cytochemistry: Official Journal of the Histochemistry Society
https://www.readbyqxmd.com/read/29734862/great-debates-in-vascular-medicine-extended-duration-anticoagulation-for-unprovoked-venous-thromboembolism-coming-to-consensus-when-the-debate-rages-on
#11
Yogendra Kanthi, Gregory Piazza
No abstract text is available yet for this article.
May 1, 2018: Vascular Medicine
https://www.readbyqxmd.com/read/29728859/up-regulation-of-hmgb1-and-tlr4-in-skin-lesions-of-lichen-planus
#12
Gabriel Costa de Carvalho, Fabiana Yasumoto Araujo Hirata, Rosana Domingues, Cristina Adelaide Figueiredo, Mariana Colombini Zaniboni, Naiura Vieira Pereira, Mirian Nacagami Sotto, Valéria Aoki, Alberto José da Silva Duarte, Maria Notomi Sato
Lichen planus (LP) is a chronic, mucocutaneous inflammatory disease of an unknown aetiology. The disease has been associated with certain viruses, and the factors such as DAMPs (damage-associated molecular patterns) and PAMPs (pathogen-associated molecular patterns) may also contribute to the inflammatory response in LP. HMGB1 (high mobility group box 1 protein) is one of the major DAMPs that induces inflammation and could trigger LP disease. The present study was aimed to examine TLR4, RAGE and HMGB1 production in epidermis or dermis by immunohistochemistry and the respective expression of these targets in the skin lesions of patients with LP...
May 4, 2018: Archives of Dermatological Research
https://www.readbyqxmd.com/read/29723156/circulating-soluble-rage-and-cell-surface-rage-on-peripheral-blood-mononuclear-cells-in-healthy-children
#13
Alberto García-Salido, Gustavo Melen, Vanesa Gómez-Piña, Gonzalo Oñoro-Otero, Ana Serrano-González, Juan Casado-Flores, Manuel Ramírez
BACKGROUND: The receptor for advanced glycation end products (RAGE) has a critical role in the pathogenesis of inflammation. In healthy children, its basal expression on the peripheral blood mononuclear cell (PBMC) and the basal circulating soluble RAGE (sRAGE) levels are unknown. The aim of this study was to describe both. METHODS: This is a monocentric, observational and descriptive study of samples obtained from healthy children. The RAGE expression on PBMC was analyzed using flow cytometry...
May 3, 2018: Journal of Pediatric Endocrinology & Metabolism: JPEM
https://www.readbyqxmd.com/read/29721599/optimization-of-magnetization-prepared-rapid-gradient-echo-mp-rage-sequence-for-neonatal-brain-mri
#14
Lili He, Jinghua Wang, Zhong-Lin Lu, Beth M Kline-Fath, Nehal A Parikh
BACKGROUND: Sequence optimization in neonates might improve detection sensitivity of abnormalities for a variety of conditions. However this has been historically challenging because tissue properties such as the longitudinal relaxation time and proton density differ significantly between neonates and adults. OBJECTIVE: To optimize the magnetization-prepared rapid gradient echo (MP-RAGE) sequence to enhance both signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) efficiencies...
May 2, 2018: Pediatric Radiology
https://www.readbyqxmd.com/read/29719300/unfractionated-heparin-alleviates-human-lung-endothelial-barrier-dysfunction-induced-by-high-mobility-group-box-1-through-regulation-of-p38-gsk3%C3%AE-snail-signaling-pathway
#15
Zhenggang Luan, Bo Hu, Lei Wu, Shanzi Jin, Xiaochun Ma, Jun Zhang, Aiping Wang
BACKGROUND/AIMS: The high mobility group box 1 (HMGB1) has been regarded as an important inflammatory mediator. Previous studies showed the involvement of HMGB1 protein in the dysfunction of endothelial barrier function during acute lung injury. However, the molecular mechanism remains unclear. METHODS: In this study, we used recombinant human HMGB1 (rhHMGB1) and HMGB1 plasmid to treat human pulmonary microvascular endothelial cell (HPMECs). We examined endothelial permeability by measuring TEER value and HRP flux...
April 26, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29714580/advancing-drug-safety-through-prospective-pharmacovigilance
#16
Peter J Pitts, Hervé Le Louet
Much has changed in a relatively short period of time. There is a raging debate over the level of evidence expected to first introduce a treatment to patients based on smaller, more adaptive data sets. Some argue for less data followed by postapproval follow-up, others for more adaptive clinical trial designs and end-point modification driven by patient-focused drug development and use of real-world evidence. The transition in both the review and postmarketing regulatory framework is happening in front of our eyes in real time...
January 1, 2018: Therapeutic Innovation & Regulatory Science
https://www.readbyqxmd.com/read/29702284/glycyrrhizin-ameliorates-atopic-dermatitis-like-symptoms-through-inhibition-of-hmgb1
#17
Ying Wang, Yue Zhang, Ge Peng, Xiuping Han
Atopic dermatitis (AD) is a chronic relapsing inflammatory skin disease prevalent worldwide. This study investigated the effects of glycyrrhizin, an extract of licorice root, on the well-established model of 2,4-dinitrochlorobenzene-induced AD-like symptoms in mice. The severity of dermatitis, histopathological changes, serum IgE levels, changes in expression of high-mobility group box 1 (HMGB1), the receptor for advanced glycation end products (RAGE), nuclear factor (NF)-κB and inflammatory cytokines were evaluated...
April 24, 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/29702126/irbesartan-attenuates-advanced-glycation-end-products-mediated-damage-in-diabetes-associated-osteoporosis-through-the-ages-rage-pathway
#18
Yan-Zhen Cheng, Shuang-Li Yang, Ji-Yu Wang, Meng Ye, Xiao-Yun Zhuo, Li-Tao Wang, Hong Chen, Hua Zhang, Li Yang
AIMS: Diabetes-associated osteoporosis is mainly caused by the formation and accumulation of advanced glycation end products (AGEs). Angiotensin II type 1 receptor blocker (ARB) has anabolic bone effects on the physicochemical properties of the bone in diabetes. We hypothesized that ARB could inhibit AGEs-induced deleterious effects. MAIN METHODS: In this study, we chose seven-week-old Leprdb/Lepr+ (db/+) and Leprdb/Leprdb (db/db) mice. After 12 week intervention by irbesartan, the microarchitecture and mechanical strength of the bone of seven-week-old db/db mice were investigated systematically...
April 24, 2018: Life Sciences
https://www.readbyqxmd.com/read/29702093/detection-of-the-receptor-for-advanced-glycation-endproducts-in-neuronally-derived-exosomes-in-plasma
#19
Sierra A Patterson, Gagan Deep, Tina E Brinkley
Exosomes are nanovesicles that participate in cell-to-cell communication and are secreted by a variety of cells including neurons. Recent studies suggest that neuronally-derived exosomes are detectable in plasma and that their contents likely reflect expression of various biomarkers in brain tissues. The receptor for advanced glycation endproducts (RAGE) has been implicated in the pathophysiology of Alzheimer's disease (AD) and is increased in brain regions affected by AD. The goal of our project was to determine whether RAGE is present in plasma exosomes, and specifically exosomes derived from neurons...
April 24, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29700775/somatostatin-maintains-permeability-and-integrity-of-blood-brain-barrier-in-%C3%AE-amyloid-induced-toxicity
#20
Seungil Paik, Rishi K Somvanshi, Ujendra Kumar
In Alzheimer's disease (AD), the impaired clearance of β-amyloid peptide (Aβ) due to disrupted tight junction and transporter proteins is the prominent cause of disease progression. Somatostatin (SST) blocks the aggregation of Aβ and inflammation whereas reduction of SST levels in the CSF and brain tissue is associated with impaired cognitive function and memory loss. However, the role of SST in preservation of blood-brain barrier (BBB) integrity and functionality in Aβ-induced toxicity is not known. In the present study using human CMEC/D3 cells, we demonstrate that SST prevents Aβ-induced BBB permeability by regulating LRP1 and RAGE expression and improving the disrupted tight junction proteins...
April 26, 2018: Molecular Neurobiology
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