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| 1 | Inflammatory pathways of importance for management of inflammatory bowel disease显示文摘Inflammatory bowel disease(IBD)is a group of chronic disorders of the gastrointestinal tract comprising Crohn’s disease(CD)and ulcerative colitis(UC).Their etiologies are unknown,but they are characterised by an imbalanced production of pro-inflammatory mediators,e.g.,tumor necrosis factor(TNF)-α,as well as increased recruitment of leukocytes to the site of inflammation.Advantages in understanding the role of the inflammatory pathways in IBD and an inadequate response to conventional therapy in a large portion of patients,has over the last two decades lead to new therapies which includes the TNF inhibitors(TNFi),designed to target and neutralise the effect of TNF-α.TNFi have shown to be efficient in treating moderate to severe CD and UC.However,convenient alternative therapeutics targeting other immune pathways are needed for patients with IBD refractory to conventional therapy including TNFi.Indeed,several therapeutics are currently under development,and have shown success in clinical trials.These include antibodies targeting and neutralising interleukin-12/23,small pharmacologic Janus kinase inhibitors designed to block intracellular signaling of several pro-inflammatory cytokines,antibodies targeting integrins,and small anti-adhesion molecules that block adhesion between leukocytes and the intestinal vascular endothelium,reducing their infiltration into the inflamed mucosa.In this review we have elucidated the major signaling pathways of clinical importance for IBD therapy and highlighted the new promising therapies available.As stated in this paper several new treatment options are under development for the treatment of CD and UC,however,no drug fits all patients.Hence,optimisations of treatment regimens are warranted for the benefit of the patients either through biomarker establishment or other rationales to maximise the effect of the broad range of mode-of-actions of the present and future drugs in IBD. | Jannie Pedersen Mehmet Coskun Christoffer Soendergaard Mohammad Salem Ole Haagen Nielsen | 2014 | World Journal of Gastroenterology2014，20，1： | 28 |
| 2 | miR-20b, miR-98, miR-125b-1*, and let-7e* as new potential diagnostic biomarkers in ulcerative colitis显示文摘AIM:To use microarray-based miRNA profiling of colonic mucosal biopsies from patients with ulcerative colitis (UC), Crohn's disease (CD), and controls in order to identify new potential miRNA biomarkers in inflammatory bowel disease. METHODS:Colonic mucosal pinch biopsies from the descending part were obtained endoscopically from patients with active UC or CD, quiescent UC or CD, as well as healthy controls. Total RNA was isolated and miRNA expression assessed using the miRNA microarray Geniom Biochip miRNA Homo sapiens (Febit GmbH, Heidelberg, Germany). Data analysis was carried out by principal component analysis and projection to latent structure-discriminant analysis using the SIMCA-P+12 software package (Umetrics, Umea, Sweden). The microarray data were subsequently validated by quantitative real-time polymerase chain reaction (qPCR) performed on colonic tissue samples from active UC patients (n = 20), patients with quiescent UC (n = 19), and healthy controls (n = 20). The qPCR results were analyzed with Mann-WhitneyU test.In silico prediction analysis were performed to identify potential miRNA target genes and the predicted miRNA targets were then compared with all UC associated susceptibility genes reported in the literature. RESULTS:The colonic mucosal miRNA transcriptome differs significantly between UC and controls, UC and CD, as well as between UC patients with mucosal inflammation and those without. However, no clear differences in the transcriptome of patients with CD and controls were found. The miRNAs with the strongest differential power were identified (miR-20b, miR-99a, miR-203, miR-26b, and miR-98) and found to be upregulated more than a 10-fold in active UC as compared to quiescent UC, CD, and controls. Two miRNAs, miR-125b-1* and let-7e*, were up-regulated more than 5-fold in quiescent UC compared to active UC, CD, and controls. Four of the seven miRNAs (miR-20b, miR-98, miR-125b-1*, and let-7e*) were validated by qPCR and found to be specifically upregulated in patients with UC. Usingin silico analysis we found several predicted pro-inflammatory target genes involved in various pathways, such as mitogen-activated protein kinase and cytokine signaling, which are both key signaling pathways in UC.CONCLUSION:The present study provides the first evidence that miR-20b, miR-98, miR-125b-1*, and let7e* are deregulated in patients with UC. The level of these miRNAs may serve as new potential biomarkers for this chronic disease. | Mehmet Coskun Jacob Tveiten Bjerrum Jakob Benedict Seidelin Jesper Thorvald Troelsen JΦrgen Olsen Ole Haagen Nielsen | 2013 | World Journal of Gastroenterology2013，19，27： | 19 |
| 3 | MicroRNAs in inflammatory bowel disease-pathogenesis,diagnostics and therapeutics显示文摘The pathogenesis of inflammatory bowel disease (IBD) is complex and largely unknown. Until recently, research has focused on the study of protein regulators in inflammation to reveal the cellular and molecular networks in the pathogenesis of IBD. However, in the last few years, new and promising insights have been generated from studies describing an association between an altered expression of a specific class of non-coding RNAs, called microRNAs (miRs or miRNAs) and IBD. The short (approximately 22 nucleotides), endogenous, single-stranded RNAs are evolutionary conserved inanimals and plants, and regulate specific target mRNAs at the post-transcriptional level. MiRNAs are involved in several biological processes, including development, cell differentiation, proliferation and apoptosis. Furthermore, it is estimated that miRNAs may be responsible for regulating the expression of nearly one-third of the genes in the human genome. Thus, miRNA deregulation often results in an impaired cellular function, and a disturbance of downstream gene regulation and signaling cascades, suggesting their implication in disease etiology. Despite the identification of more than 1900 mature human miRNAs, very little is known about their biological functions and functional targets. Recent studies have identified dysregulated miRNAs in tissue samples of IBD patients and have demonstrated similar differences in circulating miRNAs in the serum of IBD patients. Thus, there is great promise that miRNAs will aid in the early diagnosis of IBD, and in the development of personalized therapies. Here, we provide a short review of the current state-of-the-art of miRNAs in IBD pathogenesis, diagnostics and therapeutics. | Mehmet Coskun Jacob Tveiten Bjerrum Jakob Benedict Seidelin Ole Haagen Nielsen | 2012 | World Journal of Gastroenterology2012，18，34： | 18 |
| 4 | Use of thiopurines in inflammatory bowel disease显示文摘The use of thiopurines as immunosuppression for the treatment of refractory or chronic active inflammatory bowel disease is established for both Crohn's disease and ulcerative colitis.Nevertheless,many questions remain concerning the optimal treatment regimens of azathioprine,6-mercaptopurine and thioguanine.We will briefly summarize dose recommendations,indications for thiopurine therapy and side effects which are relevant in clinical practice.We discuss some currently debated topics,including the combination of azathioprine and allopurinol,switching of thiopurine therapy in case of side effects,the use of azathioprine in pregnancy,the infection risk using thiopurines and the evidence when to stop thiopurines.Excellent reviews have been published on the thiopurine metabolic pathway which will not be discussed here in detail. | Pascal Frei Luc Biedermann Ole Haagen Nielsen Gerhard Rogler | 2013 | World Journal of Gastroenterology2013，19，7： | 4 |
| 5 | Involvement of JAK/STAT signaling in the pathogenesis of inflammatory bowel disease显示文摘 | Mehmet Coskun Mohammad Salem Jannie Pedersen Ole Haagen Nielsen | 2013 | Pharmacological Research2013，，： | 3 |
| 6 | Extraintestinal manifestations of inflammatory bowel disease: Epidemiology, diagnosis, and management显示文摘 | Signe Larsen Klaus Bendtzen Ole Haagen Nielsen | 2010 | Annals of Medicine2010，，2： | 2 |
| 7 | Mucosal Healing in Ulcerative Colitis显示文摘 | Jakob Benedict Seidelin Mehmet Coskun Ole Haagen Nielsen | 2013 | Advances in Clinical Chemistry2013，，： | 2 |
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| 17 | Extraintestinal manifestations of inflammatory bowel disease: Epidemiology, diagnosis, and management显示文摘 | Signe Larsen Klaus Bendtzen Ole Haagen Nielsen | 2010 | Annals of Medicine2010，，2： | 1 |
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| 19 | Procalcitonin guid- ance and reduction of antibiotic use in acute respiratory tract infection 显示文摘 | Burkhardt O Ewig S Haagen U | 2010 | Eur Respir J2010，36，3： | 1 |
| 20 | Insulin-like Growth Factor Binding Protein 3 in Inflammatory Bowel Disease显示文摘 | Irena Kirman Richard Larry Whelan Suvinit Jain Sara Els?e Nielsen Jakob Benedict Seidelin Ole Haagen Nielsen | 2005 | Digestive Diseases and Sciences2005，，4： | 1 |
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