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Antisense anti-inflammatory

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
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
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
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
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
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
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 8, 2017: Molecular Neurobiology
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
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
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
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
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
Li Ma, Chuan-an Shen, Lei Gao, Da-wei Li, Yu-ru Shang, Kai Yin, Dong-xu Zhao, Wen-feng Cheng, Dong-qin Quan
The purpose of this present study is to prepare NF-κB/p65 antisense oligonucleotide loaded chitosan nanoparticles (NPs) and evaluate their physicochemical characterization and antisense effects in RAW264.7 macrophages. Condensed nanoparticles with mean particle size of 128±16nm, average Zeta potential of 19.6±6.3mV and high entrapment efficiency (EE) of 98.6±0.11% were formed between NF-κB/p65 antisense gene (NAG) and chitosan by complex coacervation method. Trypan blue staining and MTT tests showed that NAG chitosan NPs had no toxic effect on RAW264...
June 1, 2016: Colloids and Surfaces. B, Biointerfaces
Hidetoshi Takedatsu, Keiichi Mitsuyama, Takuji Torimura
Crohn's disease and ulcerative colitis are two important categories of human inflammatory bowel disease (IBD). Because the precise mechanisms of the inflammation and immune responses in IBD have not been fully elucidated, the treatment of IBD primarily aims to inhibit the pathogenic factors of the inflammatory cascade. Inconsistencies exist regarding the response and side effects of the drugs that are currently used to treat IBD. Recent studies have suggested that the use of nanomedicine might be advantageous for the treatment of intestinal inflammation because nano-sized molecules can effectively penetrate epithelial and inflammatory cells...
October 28, 2015: World Journal of Gastroenterology: WJG
Hong Bao, Fengying Gao, Guogang Xie, Zhenwei Liu
BACKGROUND/AIMS: Angiotensin converting enzyme 2 (ACE2) treatment suppresses the severity of acute lung injury (ALI). The effects of ACE2 in ALI have been shown to not only result from its antagonizing hydrolyzing angiotensin II (AngII), which is responsible for reduction in the vascular tension and pulmonary accumulation of inflammatory cells, but also result from a role of ACE2 in suppressing the ALI-induced apoptosis of pulmonary endothelial cells (PECs). Nevertheless, the underlying mechanisms of the role of ACE2 on PEC apoptosis are not completely understood...
2015: Cellular Physiology and Biochemistry
David E Greenberg, Daniel E Sturdevant, Kimberly R Marshall-Batty, Jessica Chu, Anthony M Pettinato, Kimmo Virtaneva, John Lane, Bruce L Geller, Stephen F Porcella, John I Gallin, Steven M Holland, Kol A Zarember
Polymorphonuclear leukocytes (PMN) from patients with chronic granulomatous disease (CGD) fail to produce microbicidal concentrations of reactive oxygen species (ROS) due to mutations in NOX2. Patients with CGD suffer from severe, life-threatening infections and inflammatory complications. Granulibacter bethesdensis is an emerging Gram-negative pathogen in CGD that resists killing by PMN of CGD patients (CGD PMN) and inhibits PMN apoptosis through unknown mechanisms. Microarray analysis was used to study mRNA expression in PMN from healthy subjects (normal PMN) and CGD PMN during incubation with G...
November 2015: Infection and Immunity
Gerhard Rogler
After a relatively long time of failed developments and negative clinical trials in pharmacological inflammatory bowel disease (IBD) therapy we now phase a time of a great number of successful studies and new therapy principles that will most likely make it into clinical practice. This will change the landscape of IBD therapy in future markedly. Many new therapeutic principles have been developed and old ones that seemed to have failed such as anti-sense technology suddenly now provide promising results. Some initially promising therapies will need further development or have failed such as Trichuris suis ova therapy (but not helminth therapy in general), CCR9 targeted therapies or recombinant IL-10...
October 2015: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Ahmed H Badawi, Paul Kiptoo, Teruna J Siahaan
Most of the current therapies used in the treatment of multiple sclerosis (MS) are either ineffective or have adverse side effects. As such, there is a need to develop better therapies that specifically target myelin-specific aberrant immune cells involved in CNS inflammation without compromising the general immune system. In the present study, we developed a new bifunctional peptide inhibitor (BPI) that is effective and specific. Our BPI (PLP-B7AP) is composed of an antigenic peptide from myelin proteolipid protein (PLP139-151) and a B7 antisense peptide (B7AP) derived from CD28 receptor...
December 2015: Journal of Multiple Sclerosis
Mark Löwenberg, Geert D'Haens
Various novel drugs have recently been evaluated in clinical trials showing promising effects in patients with inflammatory bowel disease (IBD). Here, we summarize the recent literature in the area of emerging therapies in the field of IBD, with specific focus on anti-integrin antibodies, such as vedolizumab (anti-α4β7) and etrolizumab (anti-rhuMAb β7), and the Janus kinase (JAK) inhibitor tofacitinib. Moreover, we will discuss efficacy and safety data of golimumab (a new subcutaneous anti-tumor necrosis factor (TNF) antibody), Avaxia (an orally delivered anti-TNF antibody), and Budesonide MMX; all have been developed for the treatment of ulcerative colitis...
June 2015: Current Gastroenterology Reports
Luiz C Di Stasi, Celso Ara Costa, Aline Witaicenis
INTRODUCTION: Inflammatory bowel disease (IBD) consists of Crohn's disease, ulcerative colitis and an unspecific IBD. The unclear etiology of IBD is a limiting factor that complicates the development of new pharmacological treatments and explains the high frequency of refractory patients to current drugs, including both conventional and biological therapies. In view of this, recent progress on the development of novel patented products to treat IBD was reviewed. AREAS COVERED: Evaluation of the patent literature during the period 2013 - 2014 focused on chemical compounds, functional foods and biological therapy useful for the treatment of IBD...
June 2015: Expert Opinion on Therapeutic Patents
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