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https://www.readbyqxmd.com/read/29775572/gene-therapy-with-antisense-oligonucleotides-silencing-c-myc-reduces-neointima-formation-and-vessel-wall-thickness-in-a-mouse-model-of-vein-graft-disease
#1
Christina Maria Steger, Nikolaos Bonaros, Ralf Joachim Rieker, Johannes Bonatti, Thomas Schachner
Gene therapy for avoiding intimal hyperplasia of vein grafts after coronary artery bypass grafting is still discussed controversially. A promising application of gene therapy in vein grafts is the use of antisense oligonucleotides to block the expression of genes encoding cell cycle regulatory proteins in vascular smooth muscle cells. C-myc, either directly or by regulating the expression of other proteins, controls cell proliferation, apoptosis and cell survival, tissue remodeling, angiogenesis, cell metabolism, production of inflammatory and anti-inflammatory cytokines, and also participates in cell transformation...
May 15, 2018: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/29698813/neuropathic-keratopathy
#2
REVIEW
Harminder S Dua, Dalia G Said, Elisabeth M Messmer, Maurizio Rolando, Jose M Benitez-Del-Castillo, Parwez N Hossain, Alex J Shortt, Gerd Gerling, Mario Nubile, Francisco C Figueiredo, Saaeha Rauz, Leonardo Mastropasqua, Paolo Rama, Christophe Baudouin
Neurotrophic Keratopathy (NK) refers to a condition where corneal epitheliopathy leading to frank epithelial defect with or without stromal ulceration (melting) is associated with reduced or absent corneal sensations. Sensory nerves serve nociceptor and trophic functions, which can be affected independently or simultaneously. Loss of trophic function and consequent epithelial breakdown exposes the stroma making it susceptible to enzymatic degradation. Nerve pathology can range from attrition to aberrant re-generation with corresponding symptoms from anaesthesia to hyperaesthesia/allodynia...
April 23, 2018: Progress in Retinal and Eye Research
https://www.readbyqxmd.com/read/29398253/t-cells-are-influenced-by-a-long-non-coding-rna-in-the-autoimmune-associated-ptpn2-locus
#3
Miranda Houtman, Klementy Shchetynsky, Karine Chemin, Aase Haj Hensvold, Daniel Ramsköld, Karolina Tandre, Maija-Leena Eloranta, Lars Rönnblom, Steffen Uebe, Anca Irinel Catrina, Vivianne Malmström, Leonid Padyukov
Non-coding SNPs in the protein tyrosine phosphatase non-receptor type 2 (PTPN2) locus have been linked with several autoimmune diseases, including rheumatoid arthritis, type I diabetes, and inflammatory bowel disease. However, the functional consequences of these SNPs are poorly characterized. Herein, we show in blood cells that SNPs in the PTPN2 locus are highly correlated with DNA methylation levels at four CpG sites downstream of PTPN2 and expression levels of the long non-coding RNA (lncRNA) LINC01882 downstream of these CpG sites...
February 2, 2018: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29223139/novel-treatments-for-inflammatory-bowel-disease
#4
REVIEW
Hyo Sun Lee, Soo-Kyung Park, Dong Il Park
Increased understanding of the immunopathology of inflammatory bowel disease (IBD) has led to the development of targeted therapies and has unlocked a new era in IBD treatment. The development of treatment options aimed at a variety of pathological mechanisms offers new hope for customized therapies. Beyond anti-tumor necrosis factor agents, selective lymphocyte trafficking inhibitors have been proposed as potent drugs for IBD. Among these, vedolizumab has recently been approved for both Crohn's disease and ulcerative colitis...
January 2018: Korean Journal of Internal Medicine
https://www.readbyqxmd.com/read/29175954/cd44-signaling-mediates-high-molecular-weight-hyaluronan-induced-antihyperalgesia
#5
Luiz F Ferrari, Eugen V Khomula, Dioneia Araldi, Jon D Levine
We studied, in male Sprague Dawley rats, the role of the cognate hyaluronan receptor, CD44 signaling in the antihyperalgesia induced by high molecular weight hyaluronan (HMWH). Low molecular weight hyaluronan (LMWH) acts at both peptidergic and nonpeptidergic nociceptors to induce mechanical hyperalgesia that is prevented by intrathecal oligodeoxynucleotide antisense to CD44 mRNA, which also prevents hyperalgesia induced by a CD44 receptor agonist, A6. Ongoing LMWH and A6 hyperalgesia are reversed by HMWH. HMWH also reverses the hyperalgesia induced by diverse pronociceptive mediators, prostaglandin E2 , epinephrine, TNFα, and interleukin-6, and the neuropathic pain induced by the cancer chemotherapy paclitaxel...
January 10, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29154408/chemokine-c-c-motif-ligand-25-expressed-by-trophoblast-cells-and-leukocytes-bearing-its-receptor-ccr9-an-alliance-during-embryo-implantation
#6
Rodrigo Barbano Weingrill, Mara S Hoshida, Ciro Dresch Martinhago, Simone Correa-Silva, Elaine Cardoso, Patrícia Palmeira, Claudio Romero Farias Marinho, Estela Bevilacqua
PROBLEM: We hypothesized that trophoblast expression of Ccl25 attracts a specific leukocyte cell population to the implantation site for local regulation. METHOD OF STUDY: Mice blastocysts, ectoplacental cones, and decidua at gestational days 3.5-7.5 were evaluated for Ccl25 and Ccr9 expressions. Peripheral availability and characterization of Ccr9+ leukocytes were determined by flow cytometry. Leukocyte chemotaxis was assessed in the presence of Ccl25 recombinant protein and embryos using antisense oligomers (ODNs) to Ccl25 and Ccr9 neutralizing antibody...
January 2018: American Journal of Reproductive Immunology: AJRI
https://www.readbyqxmd.com/read/29095837/resveratrol-downregulates-inflammatory-pathway-activated-by-lymphotoxin-%C3%AE-tnf-%C3%AE-in-articular-chondrocytes-comparison-with-tnf-%C3%AE
#7
COMPARATIVE STUDY
Constanze Buhrmann, Bastian Popper, Bharat B Aggarwal, Mehdi Shakibaei
While Lymphotoxin α (TNF-β), a product of lymphocytes, is known to play a pivotal role in inflammatory joint environment, resveratrol has been shown to possess anti-inflammatory and chondroprotective effects via activation of the histondeacetylase Sirt1. Whether TNF-β induction of inflammatory pathways in primary human chondrocytes (PCH) can be modulated by resveratrol, was investigated. Monolayer and alginate cultures of PCH were treated with TNF-β, anti-TNF-β, nicotinamide (NAM), antisense oligonucleotides against Sirt1 (Sirt1-ASO) and/or resveratrol and co-cultured with T-lymphocytes...
2017: PloS One
https://www.readbyqxmd.com/read/28918026/anti-fibrotic-effects-of-synthetic-oligodeoxynucleotide-for-tgf-%C3%AE-1-and-smad-in-an-animal-model-of-liver-cirrhosis
#8
Jung-Yeon Kim, Hyun-Jin An, Woon-Hae Kim, Mi-Gyeong Gwon, Hyemin Gu, Yoon-Yub Park, Kwan-Kyu Park
Liver fibrosis is characterized by changes in tissue architecture and extracellular matrix composition. Liver fibrosis affects not only hepatocytes but also the non-parenchymal cells such as hepatic stellate cells (HSCs), which are essential for maintaining an intact liver structure and function. Transforming growth factor β1 (TGF-β1) is a multifunctional cytokine that induces liver fibrosis through activation of Smad signaling pathways. To improve a new therapeutic approach, synthetic TGF-β1/Smad oligodeoxynucleotide (ODN) was used to suppress both TGF-β1 expression and Smad transcription factor using a combination of antisense ODN and decoy ODN...
September 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28628078/nociceptor-interleukin-10-receptor-1-is-critical-for-muscle-analgesia-induced-by-repeated-bouts-of-eccentric-exercise-in-the-rat
#9
Pedro Alvarez, Oliver Bogen, Paul G Green, Jon D Levine
Delayed-onset muscle soreness is typically observed after strenuous or unaccustomed eccentric exercise. Soon after recovery, blunted muscle soreness is observed on repeated eccentric exercise, a phenomenon known as repeated bout effect (RBE). Although regular physical activity decreases muscle hyperalgesia, likely because of increased production of the anti-inflammatory cytokine interleukin-10 (IL-10) in the skeletal muscle, whether IL-10 also contributes to the antinociceptive effect of RBE is unknown. Furthermore, whether IL-10 attenuates muscle hyperalgesia by acting on muscle nociceptors remains to be established...
August 2017: Pain
https://www.readbyqxmd.com/read/28606878/resolution-of-inflammation-in-inflammatory-bowel-disease
#10
REVIEW
Gerhard Rogler
Treatment of inflammatory bowel disease at present mainly targets mediators of inflammation to stop or suppress pro-inflammatory processes. Typical examples are steroids, suppression of T cells by thioguanine nucleotides, or antibodies against cytokines such as tumour necrosis factor, interleukin 12, or interleukin 23. In addition to suppression of inflammation, development of therapeutic strategies that support resolution of inflammation or that actively resolve inflammation might be desirable. Resolution of inflammation is now seen as an active process involving specific mediators (eg, lipid mediators or specific cytokines) that is mandatory to restore organ function and completely shut down inflammation...
July 2017: Lancet. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28599923/silencing-of-the-rna-binding-protein-hur-attenuates-hyperalgesia-and-motor-disability-in-experimental-autoimmune-encephalomyelitis
#11
Maria Domenica Sanna, Alessandro Quattrone, Nicoletta Galeotti
Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system associated with progressive neuronal loss and axonal degeneration. Neuronal lesions and dysfunction lead often to neuropathic pain, the most prevalent and difficult to treat pain syndrome observed in MS patients. Despite its widespread occurrence, the underlying neural mechanisms for MS pain are not fully understood. For a better clarification of the pathophysiology of MS-associated pain, we investigated the role of HuR, an RNA-binding protein that positively regulates the stability of many target mRNAs, including several cytokines...
September 1, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28486793/inflammatory-bowel-disease-updates-on-molecular-targets-for-biologics
#12
REVIEW
Konstantinos H Katsanos, Konstantinos A Papadakis
Therapy for inflammatory bowel disease (IBD) has changed, with several new agents being evaluated. The era of anti-tumor necrosis factor (anti-TNF) antibody therapy saw remarkable progress in IBD therapy. Some patients, however, do not respond to anti-TNF treatment, or their response decreases over time. This phenomenon highlights the need to identify new molecular targets for therapy in IBD. The targets of new therapeutic molecules in IBD must aim to restore immune dysregulation by the inhibition of proinflammatory cytokines (TNF-α, interleukin [IL]-6, IL-13, IL-17, IL-18, and IL-21) and augmentation of the effect of anti-inflammatory cytokines (IL-10, IL-11, and transforming growth factor β) and to pursue new anti-inflammatory targets, such as regulatory T-cell therapy, Smad7 antisense, Janus-activated kinase inhibition, Toll-like receptor stimulation, leukocyte adhesion, and blockade of T-cell homing via integrins and mucosal addressin cellular adhesion molecule-1...
July 15, 2017: Gut and Liver
https://www.readbyqxmd.com/read/28334721/microrna-9-inhibits-nlrp3-inflammasome-activation-in-human-atherosclerosis-inflammation-cell-models-through-the-jak1-stat-signaling-pathway
#13
Yue Wang, Zhihua Han, Yuqi Fan, Junfeng Zhang, Kan Chen, Lin Gao, Huasu Zeng, Jiatian Cao, Changqian Wang
BACKGROUND/AIMS: MicroRNA-9 (miR-9) is involved in inflammatory reaction in atherosclerosis; however, its function and regulatory mechanisms remain unclear. We aimed to uncover the exact roles of miR-9 and downstream signaling pathways using in vitro human atherosclerosis models. METHODS: We used oxidized low-density lipoprotein (oxLDL)-stimulated human THP-1 derived macrophages, oxLDL-stimulated human primary peripheral blood monocytes and lipopolysaccharides (LPS) or Alum-stimulated human THP-1 derived macrophages as in vitro atherosclerosis inflammation models...
2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28209997/antisense-mir-132-blockade-via-the-ache-r-splice-variant-mitigates-cortical-inflammation
#14
Nibha Mishra, Lyndon Friedson, Geula Hanin, Uriya Bekenstein, Meshi Volovich, Estelle R Bennett, David S Greenberg, Hermona Soreq
MicroRNA (miR)-132 brain-to-body messages suppress inflammation by targeting acetylcholinesterase (AChE), but the target specificity of 3'-AChE splice variants and the signaling pathways involved remain unknown. Using surface plasmon resonance (SPR), we identified preferential miR-132 targeting of soluble AChE-R over synaptic-bound AChE-S, potentiating miR-132-mediated brain and body cholinergic suppression of pro-inflammatory cytokines. Inversely, bacterial lipopolysaccharide (LPS) reduced multiple miR-132 targets, suppressed AChE-S more than AChE-R and elevated inflammatory hallmarks...
February 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28181190/distribution-of-alox15-in-the-rat-brain-and-its-role-in-prefrontal-cortical-resolvin-d1-formation-and-spatial-working-memory
#15
Suku-Maran Shalini, Christabel Fung-Yih Ho, Yee-Kong Ng, Jie-Xin Tong, Eng-Shi Ong, Deron R Herr, Gavin S Dawe, Wei-Yi Ong
Docosahexaenoic acid (DHA) is enriched in membrane phospholipids of the central nervous system (CNS) and has a role in aging and neuropsychiatric disorders. DHA is metabolized by the enzyme Alox15 to 17S-hydroxy-DHA, which is then converted to 7S-hydroperoxy,17S-hydroxy-DHA by a 5-lipoxygenase, and thence via epoxy intermediates to the anti-inflammatory molecule, resolvin D1 (RvD1 or 7S,8R,17S-trihydroxy-docosa-Z,9E,11E,13Z,15E,19Z-hexaenoic acid). In this study, we investigated the distribution and function of Alox15 in the CNS...
February 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/28106744/oligonucleotide-therapy-for-obstructive-and-restrictive-respiratory-diseases
#16
REVIEW
Wupeng Liao, Jinrui Dong, Hong Yong Peh, Lay Hong Tan, Kah Suan Lim, Li Li, Wai-Shiu Fred Wong
Inhaled oligonucleotide is an emerging therapeutic modality for various common respiratory diseases, including obstructive airway diseases like asthma and chronic obstructive pulmonary disease (COPD) and restrictive airway diseases like idiopathic pulmonary fibrosis (IPF). The advantage of direct accessibility for oligonucleotide molecules to the lung target sites, bypassing systemic administration, makes this therapeutic approach promising with minimized potential systemic side effects. Asthma, COPD, and IPF are common chronic respiratory diseases, characterized by persistent airway inflammation and dysregulated tissue repair and remodeling, although each individual disease has its unique etiology...
January 17, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/27903030/-novel-therapeutic-approaches-in-inflammatory-bowel-diseases
#17
REVIEW
Raja Atreya, Markus Friedrich Neurath
Increasing knowledge regarding the immunopathogenesis of IBD has led to the development or approval of novel therapeutic agents for the treatment of Crohn's disease or ulcerative colitis. The new substances for example include antibodies against IL-12 / 23, anti-adhesion molecules and antisense oligonucleotides. The increase of therapeutic options will lead to a change of currently used therapeutic algorithms. Biomarkers to ensure a more individualized therapeutic approach are urgently needed to improve an efficient therapy of IBD patients...
November 2016: Deutsche Medizinische Wochenschrift
https://www.readbyqxmd.com/read/27832357/emerging-biologics-in-inflammatory-bowel-disease
#18
REVIEW
Heyson Chi-Hey Chan, Siew Chien Ng
Early biologic therapy is recommended in patients with inflammatory bowel disease and poor prognostic factors and in those refractory to conventional medications. Anti-tumor necrosis factor (anti-TNF) agents are the most commonly used biologic agents. However, some patients may not have an initial response to anti-TNF therapy, and one-third will develop loss of response over time. Anti-TNF drugs can also be associated with side effects. In addition, the use of biologics is currently limited by their cost, especially in developing countries...
February 2017: Journal of Gastroenterology
https://www.readbyqxmd.com/read/27042137/recent-insights-into-the-molecular-pathogenesis-of-crohn-s-disease-a-review-of-emerging-therapeutic-targets
#19
REVIEW
Teodora-Ecaterina M Manuc, Mircea M Manuc, Mircea M Diculescu
Chronic inflammatory bowel diseases (IBDs) are a subject of great interest in gastroenterology, due to a pathological mechanism that is difficult to explain and an optimal therapeutic approach still undiscovered. Crohn's disease (CD) is one of the main entities in IBD, characterized by clinical polymorphism and great variability in the treatment response. Modern theories on the pathogenesis of CD have proven that gut microbiome and environmental factors lead to an abnormal immune response in a genetically predisposed patient...
2016: Clinical and Experimental Gastroenterology
https://www.readbyqxmd.com/read/26981216/novel-epigenetic-based-therapies-useful-in-cardiovascular-medicine
#20
REVIEW
Claudio Napoli, Vincenzo Grimaldi, Maria Rosaria De Pascale, Linda Sommese, Teresa Infante, Andrea Soricelli
Epigenetic modifications include DNA methylation, histone modifications, and microRNA. Gene alterations have been found to be associated with cardiovascular diseases, and epigenetic mechanisms are continuously being studied to find new useful strategies for the clinical management of afflicted patients. Numerous cardiovascular disorders are characterized by the abnormal methylation of CpG islands and so specific drugs that could inhibit DNA methyltransferase directly or by reducing its gene expression (e.g...
February 26, 2016: World Journal of Cardiology
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