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https://www.readbyqxmd.com/read/27903030/-novel-therapeutic-approaches-in-inflammatory-bowel-diseases
#1
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
#2
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...
November 10, 2016: 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
#3
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
#4
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
https://www.readbyqxmd.com/read/26970817/anti-inflammatory-activity-of-chitosan-nanoparticles-carrying-nf-%C3%AE%C2%BAb-p65-antisense-oligonucleotide-in-raw264-7-macropghage-stimulated-by-lipopolysaccharide
#5
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
https://www.readbyqxmd.com/read/26525603/nanomedicine-and-drug-delivery-strategies-for-treatment-of-inflammatory-bowel-disease
#6
REVIEW
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
https://www.readbyqxmd.com/read/26356266/angiotensin-converting-enzyme-2-inhibits-apoptosis-of-pulmonary-endothelial-cells-during-acute-lung-injury-through-suppressing-mir-4262
#7
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
https://www.readbyqxmd.com/read/26283340/simultaneous-host-pathogen-transcriptome-analysis-during-granulibacter-bethesdensis-infection-of-neutrophils-from-healthy-subjects-and-patients-with-chronic-granulomatous-disease
#8
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
https://www.readbyqxmd.com/read/26277232/where-are-we-heading-to-in-pharmacological-ibd-therapy
#9
REVIEW
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
https://www.readbyqxmd.com/read/26140285/immune-tolerance-induction-against-experimental-autoimmune-encephalomyelitis-eae-using-a-new-plp-b7ap-conjugate-that-simultaneously-targets-b7-cd28-costimulatory-signal-and-tcr-mhc-ii-signal
#10
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
https://www.readbyqxmd.com/read/26031830/next-generation-therapeutics-for-ibd
#11
REVIEW
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
https://www.readbyqxmd.com/read/25944127/products-for-the-treatment-of-inflammatory-bowel-disease-a-patent-review-2013-2014
#12
REVIEW
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
https://www.readbyqxmd.com/read/25911184/antisense-approach-to-inflammatory-bowel-disease-prospects-and-challenges
#13
REVIEW
Irene Marafini, Davide Di Fusco, Emma Calabrese, Silvia Sedda, Francesco Pallone, Giovanni Monteleone
Despite the great success of anti-tumour necrosis factor-based therapies, the treatment of Crohn's disease (CD) and ulcerative colitis (UC) still remains a challenge for clinicians, as these drugs are not effective in all patients, their efficacy may wane with time, and their use can increase the risk of adverse events and be associated with the development of new immune-mediated diseases. Therefore, new therapeutic targets are currently being investigated both in pre-clinical studies and in clinical trials...
May 2015: Drugs
https://www.readbyqxmd.com/read/25772532/dna-enzymes-as-potential-therapeutics-towards-clinical-application-of-10-23-dnazymes
#14
REVIEW
Alesya A Fokina, Dmitry A Stetsenko, Jean-Christophe François
INTRODUCTION: Ongoing studies on the inhibition of gene expression at the mRNA level have identified several types of specific inhibitors such as antisense oligonucleotides, small interfering RNA, ribozymes and DNAzymes (Dz). After its discovery in 1997, the 10-23 Dz (which can cleave RNA efficiently and site-specifically, has flexible design, is independent from cell mechanisms, does not require expensive chemical modifications for effective use in vivo) has been employed to downregulate a range of therapeutically important genes...
May 2015: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/25729432/current-new-and-future-biological-agents-on-the-horizon-for-the-treatment-of-inflammatory-bowel-diseases
#15
REVIEW
Aurelien Amiot, Laurent Peyrin-Biroulet
Biological agents for inflammatory bowel diseases (IBD) targeting tumor necrosis factor (TNF) have changed the way to treat IBD refractory to standard medications and allowed us to reach new therapeutic goals such as mucosal healing and deep remission. A better understanding of the components of the pathological processes that are a hallmark of IBD has led to the development of a new family of biological agents in Crohn's disease and ulcerative colitis. Biosimilars, which are copy versions of currently licensed biological agents, will be soon available...
March 2015: Therapeutic Advances in Gastroenterology
https://www.readbyqxmd.com/read/25701029/an-orally-administrated-nucleotide-delivery-vehicle-targeting-colonic-macrophages-for-the-treatment-of-inflammatory-bowel-disease
#16
Zhen Huang, Jingjing Gan, Lixin Jia, Guangxing Guo, Chunming Wang, Yuhui Zang, Zhi Ding, Jiangning Chen, Junfeng Zhang, Lei Dong
Tumor necrosis factor-alpha (TNF-α) plays a central role in the pathogenesis of inflammatory bowel disease (IBD). Anti-TNF-α therapies have shown protective effects against colitis, but an efficient tool for target suppression of its secretion - ideally via oral administration - remains in urgent demand. In the colon tissue, TNF-α is mainly secreted by the colonic macrophages. Here, we report an orally-administrated microspheric vehicle that can target the colonic macrophages and suppress the local expression of TNF-α for IBD treatment...
April 2015: Biomaterials
https://www.readbyqxmd.com/read/25447409/epithelial-mesenchymal-transition-and-cancer-stem-cells-mediated-by-a-long-non-coding-rna-hotair-are-involved-in-cell-malignant-transformation-induced-by-cigarette-smoke-extract
#17
Yi Liu, Fei Luo, Yuan Xu, Bairu Wang, Yue Zhao, Wenchao Xu, Le Shi, Xiaolin Lu, Qizhan Liu
The incidence of lung diseases, including cancer, caused by cigarette smoke is increasing, but the molecular mechanisms of gene regulation induced by cigarette smoke remain unclear. This report describes a long noncoding RNA (lncRNA) that is induced by cigarette smoke extract (CSE) and experiments utilizing lncRNAs to integrate inflammation with the epithelial-mesenchymal transition (EMT) in human bronchial epithelial (HBE) cells. The present study shows that, induced by CSE, IL-6, a pro-inflammatory cytokine, leads to activation of STAT3, a transcription activator...
January 1, 2015: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/25260583/clinical-features-and-pathobiology-of-ebolavirus-infection
#18
REVIEW
Aftab A Ansari
There has clearly been a deluge of international press coverage of the recent outbreak of Ebolavirus in Africa and is partly related to the "fear factor" that comes across when one is confronted with the fact that once infected, not only is the speed of death in a majority of cases rapid but also the images of the cause of death such as bleeding from various orifices gruesome and frightening. The fact that it leads to infection and death of health care providers (10% during the current epidemic) and the visualization of protective gear worn by these individuals to contain such infection adds to this "fear factor"...
December 2014: Journal of Autoimmunity
https://www.readbyqxmd.com/read/25244011/knock-down-of-il-1ra-in-obese-mice-decreases-liver-inflammation-and-improves-insulin-sensitivity
#19
Niclas Franck, Michael Maris, Sarah Nalbandian, Saswata Talukdar, Simon Schenk, Hans-Peter Hofmann, David Bullough, Olivia Osborn
Interleukin 1 Receptor antagonist (IL-1Ra) is highly elevated in obesity and is widely recognized as an anti-inflammatory cytokine. While the anti-inflammatory role of IL-1Ra in the pancreas is well established, the role of IL-1Ra in other insulin target tissues and the contribution of systemic IL-1Ra levels to the development of insulin resistance remains to be defined. Using antisense knock down of IL-1Ra in vivo, we show that normalization of IL-1Ra improved insulin sensitivity due to decreased inflammation in the liver and improved hepatic insulin sensitivity and these effects were independent of changes in body weight...
2014: PloS One
https://www.readbyqxmd.com/read/25219927/modulation-of-%C3%AE-2-msh-hepatoprotection-by-antisense-peptides-and-melanocortin-subtype-3-and-4-receptor-antagonists
#20
Petra Turcic, Nikola Stambuk, Pasko Konjevoda, Tomislav Kelava, Mario Gabricevic, Ranko Stojkovic, Gorana Aralica
Melanocortins, i.e., melanocyte stimulating hormones (MSH) are peptides with strong antiinflammatory effects. The most investigated aspects of γ2-MSH are related to cardiovascular effects and natriuresis, with limited research available about its anti-inflammatory and cytoprotective effects. The aims of this study were: 1) to examine the effects of γ2-MSH and its derivative [D-Trp(8)]-γ2-MSH on the acetaminophen model of liver damage in CBA mice; 2) to evaluate the modulation of γ2-MSH hepatoprotection by melanocortin subtypes 3 and 4 receptor antagonists SHU 9119 and HS 024; 3) to define the importance of central MSH pharmacophore region (HFRW) by using antisense peptides LVKAT and VKAT...
2015: Medicinal Chemistry
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