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Sho-Ichi Yamagishi, Takanori Matsui, Yuji Ishibashi, Fumiyuki Isami, Yumi Abe, Tatsuya Sakaguchi, Yuichiro Higashimoto
Reducing sugars can react non-enzymatically with amino groups of proteins and lipids to form irreversibly cross-linked macroprotein derivatives called as advanced glycation end products (AGEs). Cross-linking modification of extracellular matrix proteins by AGEs deteriorate their tertiary structural integrity and function, contributing to aging-related organ damage and diabetes-associated complications, such as cardiovascular disease (CVD). Moreover, engagement of receptor for AGEs, RAGE with the ligands evoke oxidative stress generation and inflammatory, thrombotic and fibrotic reactions in various kinds of tissues, further exacerbating the deleterious effects of AGEs on multiple organ systems...
October 21, 2016: Current Pharmaceutical Design
Xiao-Bin Fang, Ying-Qi Xu, Hon-Fai Chan, Chun-Ming Wang, Qing Zheng, Fei Xiao, Mei-Wan Chen
Hepatocellular carcinoma (HCC) is an aggressive malignancy and the second leading cause of cancer death worldwide. Most current therapeutic agents lack the tumor-targeting efficiency and result in a nonselective biodistribution in the body. In our previous study, we identified a peptide Ala-Pro-Asp-Thr-Lys-Thr-Gln (APDTKTQ) that can selectively bind to the receptor of advanced glycation end-products (RAGE), an immunoglobulin superfamily cell surface molecule overexpressed during HCC malignant progression. Here, we report the design of a mixed micelles system modified with this peptide to target HCC cells...
October 21, 2016: Molecular Pharmaceutics
Kailash Prasad, Abdullah Sarkar, Mohammad A Zafar, Ahmed Shoker, Hamdi Ei Moselhi, Maryann Tranquilli, Bulat A Ziganshin, John A Elefteriades
BACKGROUND: Matrix metalloproteinases (MMPs) have been implicated in the pathogenesis of thoracic aortic aneurysms (TAAs). Cytokines [Interleukin (IL)-Iβ, IL-2, IL-6, and TNF-α)] increase the expression of MMP-2 and -3. Advanced glycation end products (AGEs) interact with cell receptors to increase the release of cytokines. Circulating soluble receptors for AGEs (sRAGE) and endogenous secretory RAGE (esRAGE) compete with membrane bound RAGE for binding with AGEs and reduce the production of cytokines...
February 2016: Aorta (Stamford, Conn.)
Min-Soo Kim, Ji Hye Bang, Jun Lee, Jung-Soo Han, Tae Gon Baik, Won Kyung Jeon
BACKGROUND: Ginkgo biloba extract (GBE)-a widely used nutraceutical-is reported to have diverse functions, including positive effects on memory and vasodilatory properties. Although numerous studies have assessed the neuroprotective properties of GBE in ischemia, only a few studies have investigated the neuro-pharmacological mechanisms of action of GBE in chronic cerebral hypoperfusion (CCH). PURPOSE: In the present study, we sought to determine the effects of GBE on CCH-induced neuroinflammation and cholinergic dysfunction in a rat model of bilateral common carotid artery occlusion (BCCAo)...
November 15, 2016: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Zhong'e Zhou, Yong Tang, Xian Jin, Chengjun Chen, Yi Lu, Liang Liu, Chengxing Shen
Advanced glycation end products (AGEs) are major inflammatory mediators in diabetes, affecting atherosclerosis progression via macrophages. Metformin slows diabetic atherosclerosis progression through mechanisms that remain to be fully elucidated. The present study of murine bone marrow derived macrophages showed that (1) AGEs enhanced proinflammatory cytokines (interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α)) mRNA expression, RAGE expression, and NFκB activation; (2) metformin pretreatment inhibited AGEs effects and AGEs-induced cluster designation 86 (CD86) (M1 marker) expression, while promoting CD206 (M2 marker) surface expression and anti-inflammatory cytokine (IL-10) mRNA expression; and (3) the AMPK inhibitor, Compound C, attenuated metformin effects...
2016: Journal of Diabetes Research
Nabanita Das, Varun Dewan, Peter M Grace, Robin J Gunn, Ryo Tamura, Netanel Tzarum, Linda R Watkins, Ian A Wilson, Hang Yin
Infectious and sterile inflammatory diseases are correlated with increased levels of high mobility group box 1 (HMGB1) in tissues and serum. Extracellular HMGB1 is known to activate Toll-like receptors (TLRs) 2 and 4 and RAGE (receptor for advanced glycation endproducts) in inflammatory conditions. Here, we find that TLR5 is also an HMGB1 receptor that was previously overlooked due to lack of functional expression in the cell lines usually used for studying TLR signaling. HMGB1 binding to TLR5 initiates the activation of NF-κB signaling pathway in a MyD88-dependent manner, resulting in proinflammatory cytokine production and pain enhancement in vivo...
October 18, 2016: Cell Reports
Suzanne Miller, Amanda P Henry, Emily Hodge, Alexander K Kheirallah, Charlotte K Billington, Tracy L Rimington, Sangita K Bhaker, Ma'en Obeidat, Erik Melén, Simon K Merid, Caroline Swan, Catherine Gowland, Carl P Nelson, Ceri E Stewart, Charlotte E Bolton, Iain Kilty, Anders Malarstig, Stuart G Parker, Miriam F Moffatt, Andrew J Wardlaw, Ian P Hall, Ian Sayers
INTRODUCTION: Genome-Wide Association Studies have identified associations between lung function measures and Chronic Obstructive Pulmonary Disease (COPD) and chromosome region 6p21 containing the gene for the Advanced Glycation End Product Receptor (AGER, encoding RAGE). We aimed to (i) characterise RAGE expression in the lung, (ii) identify AGER transcripts, (iii) ascertain if SNP rs2070600 (Gly82Ser C/T) is associated with lung function and serum sRAGE levels and (iv) identify whether the Gly82Ser variant is functionally important in altering sRAGE levels in an airway epithelial cell model...
2016: PloS One
Jan Filipovsky, Jitka Seidlerova, Otto Mayer, Petra Karnosova
OBJECTIVE: Accumulation of advanced glycation end-products (AGE) has been suggested to be involved in several pathophysiological processes in the vessel wall. Soluble isoform of receptor for AGE (sRAGE) acts as a decoy for capturing circulating AGE, thus preventing them from binding to the cell-surface receptor (RAGE) and protecting against the RAGE-AGE axis-elicited processes. We hypothesized that low sRAGE levels might be associated with increased arterial stiffness. DESIGN AND METHOD: In a cross-sectional design, we analyzed 1077 subjects, aged 25 to 64 years, from the Czech population-based study ("Post-MONICA")...
September 2016: Journal of Hypertension
Magdalena Pertynska-Marczewska, Evanthia Diamanti-Kandarakis
OBJECTIVE: The hypothalamic gonadotropin-releasing hormone pulse generator, the pituitary gonadotropes, the ovaries, and the uterus play a crucial role in female fertility. A decline in reproductive performance represents a complex interplay of actions at all levels of the hypothalamic-pituitary-ovarian axis. Recently, in the field of female reproductive aging attention is drawn to the carbonyl stress theory. Advanced glycation end products (AGEs) contribute directly to protein damage, induce a chain of oxidative stress (OS) reactions, and increase inflammatory reactions...
October 3, 2016: Menopause: the Journal of the North American Menopause Society
Po-Chun Chang, Yi-Chi Chao, Meng-Hsuan Hsiao, Hao-Syun Chou, Yi-Han Jheng, Xin-Hong Yu, Ning Lee, Connie Yang, Dean-Mo Liu
BACKGROUND: Developing a drug carrier with favorable handling characteristics that can respond to environmental changes following inflammation, such as pH changes, may be beneficial for treating periodontitis. This study aimed to investigate the preclinical feasibility of using naringin, a naturally derived polymethoxylated flavonoid compound with anti-inflammatory properties, to inhibit periodontitis induction via a thermo-gelling and pH-responsive injectable hydrogel. METHODS: The hydrogel was made of amphipathic carboxymethyl-hexanoyl chitosan (CHC), beta glycerol-phosphate (β-GP), and glycerol, and the thermo-gelling and pH-responsive characteristics of the hydrogel as well as the cell viability after treatment with the hydrogel containing naringin were evaluated in vitro...
October 14, 2016: Journal of Periodontology
Christoph Tondera, Markus Laube, Jens Pietzsch
The EF-hand type calcium-binding protein S100A12 exerts numerous intra- and extracellular functions of (patho)physiological relevance. Therefore, receptors of S100A12 are of high interest for research and clinical applications. Beside the extensively studied receptor for advanced glycation endproducts (RAGE), G-protein coupled receptors and more recently, scavenger receptors are suggested to be putative S100A12 receptors. Own findings and further information from the literature predestined CD36, a class B scavenger receptor, as promising candidate...
October 12, 2016: Amino Acids
Jianjun Gu, Rong Xu, Yaxing Li, Jianhe Zhang, Shousen Wang
To explore the effects of microRNA-218 (miR-218) on glioma cell lines and the related mechanism. U251 and U87 cells were transfected with negative control, miR-218 mimic or miR-218 inhibitor using lipofectamine 2000. The expressions of mRNA and proteins were detected with qRT-PCR and Western blotting. The cell proliferation, apoptosis, migration and invasion were studied using MTT, flow cytometry, Transwell assay and scratch-wound assay, respectively. The targeting effect of HMGB1 by miR-218 was measured with luciferase reporter assay...
2016: American Journal of Translational Research
Jae-Hwan Lee, Hyun-Sook Kim, Jae-Hyeong Park, Min Su Kim, Byung Joo Sun, Seung Ryu, Song Soo Kim, Seon Ah Jin, Jun Hyung Kim, Si Wan Choi, Jin-Ok Jeong, In-Sun Kwon, In-Whan Seong
BACKGROUND AND OBJECTIVES: Carbon monoxide (CO) poisoning can cause tissue hypoxia and left ventricular systolic dysfunction (LVSD) requiring intensive medical management. Our objectives were to find incidence and clinical course of LVSD CO intoxicated patients and make a clinical scoring to predict LVSD. SUBJECTS AND METHODS: We included all consecutive patients with CO exposure in the emergency room. LVSD was defined by LVEF <50% assessed by echocardiography...
September 2016: Korean Circulation Journal
Aleem Syed, Qiaochu Zhu, Emily A Smith
The effect of ligand on the lateral diffusion of receptor for advanced glycation endproducts (RAGE), a receptor involved in numerous pathological conditions, remains unknown. Single particle tracking experiments that use quantum dots specifically bound to hemagglutinin (HA)-tagged RAGE (HA-RAGE) are reported to elucidate the effect of ligand binding on HA-RAGE diffusion in GM07373 cell membranes. The ligand used in these studies is methylglyoxal modified-bovine serum albumin (MGO-BSA) containing advanced glycation end products modifications...
October 7, 2016: Biochimica et Biophysica Acta
Kailash Prasad, Shuchita Tiwari
Advanced glycation end products (AGEs) are heterogeneous group of molecules formed from non-enzymatic reaction of reducing sugars with amino group of proteins, lipids, and nucleic acid. Interaction of AGEs with its cell-bound receptor (RAGE) results in generation of oxygen radicals, nuclear factor kappa-β, pro-inflammatory cytokines and cell adhesion molecules, and is involved in the pathophysiology of cardiovascular diseases (CVD). Circulating soluble forms of RAGE (sRAGE) and endo-secretory RAGE (esRAGE) compete with RAGE for ligand binding and function as a decoy...
October 6, 2016: Current Pharmaceutical Design
M Aletti, H Savini, C Ficko, J Bordes, A Cambon, M Billhot, G Velut, H Granier, T De Greslan, T Carmoi
The clinical spectrum of Ebola virus disease (EVD) ranges from very serious forms with organ failure and death within days to paucisymptomatic forms and perhaps even asymptomatic. The authors propose a focus on the clinical manifestations of EVD, on prognosis and on therapeutic aspects (excluding resuscitation). This work extracts from the literature the main data gathered during the 2014-2015 epidemic that raged in Guinea Conakry and Sierra Leone. These two countries, even if they are separated by a border, are one and the same population base...
October 4, 2016: La Revue de Médecine Interne
Kayoko Waki, Akira Yamada
High Mobility Group Box 1 (HMGB1) is a member of the damage-associated molecular patterns (DAMPs), which cause inflammation and trigger innate immunity through Toll-like receptors (TLRs) 2/4 and the receptor for advanced glycation end products (RAGE). We examined the effect of glycyrrhizin, a selective inhibitor of HMGB1, on the induction of cytotoxic T-lymphocytes (CTLs) in mice. B6 mice, either OT-1 spleen cell-transferred or untransferred, were immunized with an s.c. injection of OVA257-264 peptide with topical imiquimod, and glycyrrhizin was mixed with the antigen peptide...
September 22, 2016: Cancer Science
Chunyan Yang, Yulong Song, Hui Wang
The present study aimed to investigate the protective role of ketamine in lipopolysaccharide (LPS)-induced acute lung injury (ALI) by the inhibition of the receptor for advanced glycation end products (RAGE) and toll-like receptor 9 (TLR9). ALI was induced in rats by intratracheal instillation of LPS (5 mg/kg), and ketamine (5, 7.5, and 10 mg/kg) was injected intraperitoneally 1 h after LPS administration. Meanwhile, A549 alveolar epithelial cells were incubated with LPS in the presence or absence of ketamine...
October 7, 2016: Journal of Investigative Surgery: the Official Journal of the Academy of Surgical Research
Kailash Prasad, Indu Dhar, Qifeng Zhou, Hamdi Elmoselhi, Muhammad Shoker, Ahmed Shoker
Interaction of advanced glycation end products (AGEs) with its cell-bound receptor (RAGE) results in cell dysfunction through activation of nuclear factor kappa-B, increase in expression and release of inflammatory cytokines, and generation of oxygen radicals. Circulating soluble receptors, soluble receptor (sRAGE), endogenous secretory receptor (esRAGE) and cleaved receptor (cRGAE) act as decoy for RAGE ligands and thus have cytoprotective effects. Low levels of sRAGE and esRAGE have been proposed as biomarkers for many diseases...
October 6, 2016: Molecular and Cellular Biochemistry
Sayeed Ahmad, Salman Akhtar, Qazi Mohammad Sajid Jamal, Syed Mohd Danish Rizvi, Mohammad A Kamal, M Kalim A Khan, Mohd Haris Siddiqui
AD is a progressive and irreversible neurodegenerative disease and the most common cause of dementia in the elderly population. Βeta- amyloid cascade formation along with several cytoskeleton abnormalities succeeding to the hyperphosphorylation of microtubule-associated tau protein in neurons leads to the elicitation of several neurotoxic incidents. As an outcome of these phenomena, steady growth of dementia in aged population is becoming ubiquitous in both developed and developing countries. Thus, the key aspiration is to endow with stable daily life functionality to the person suffering from dementia and to cut down or slower the symptoms of disease leading to disruptive behavior...
October 3, 2016: CNS & Neurological Disorders Drug Targets
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