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Use of thiopurines in inflammatory bowel disease

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World Journal of Gastroenterology 2013年第7期19卷 1040-1048页

作者： Pascal Frei Luc Biedermann ole Haagen nielsen Gerhard Rogler Division of Gastroenterology and Hepatology Department of Internal MedicineUniversity Hospital of ZürichCH-8091 ZürichSwitzerland Department of Gastroenterology Medical SectionHerlev HospitalUniversity of CopenhagenDK-2730 HerlevDenmark

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 ***,many questions remain concerning the optimal treatment regimens of azathioprine,6-mercaptopurine and *** will briefly summarize dose recommendations,indications for thiopurine therapy and side effects which are relevant in clinical *** 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 *** reviews have been published on the thiopurine metabolic pathway which will not be discussed here in detail.

关键词： Thiopurines Inflammatory bowel disease Crohn’s disease Ulcerative colitis Immunosuppression Infection

The impact of genotyping strategies and statistical models on accuracy of genomic prediction for survival in pigs

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Journal of Animal Science and Biotechnology 2023年第3期14卷 908-916页

作者： Tianfei Liu bjarne nielsen ole F.Christensen Mogens SandøLund Guosheng Su Institute of Animal Science Guangdong Academy of Agricultural SciencesGuangzhou 510640China Center for Quantitative Genetics and Genomics Aarhus University8830 TjeleDenmark Pig Research Centre SEGES1609 CopenhagenDenmark

Background:Survival from birth to slaughter is an important economic trait in commercial pig *** survival can improve both economic efficiency and animal *** aim of this study is to explore the impact of genotyping strategies and statistical models on the accuracy of genomic prediction for survival in pigs during the total growing period from birth to ***:We simulated pig populations with different direct and maternal heritabilities and used a linear mixed model,a logit model,and a probit model to predict genomic breeding values of pig survival based on data of individual survival records with binary outcomes(0,1).The results show that in the case of only alive animals having genotype data,unbiased genomic predictions can be achieved when using variances estimated from pedigreebased *** using genomic information achieved up to 59.2%higher accuracy of estimated breeding value compared to pedigree-based model,dependent on genotyping *** scenario of genotyping all individuals,both dead and alive individuals,obtained the highest *** an equal number of individuals(80%)were genotyped,random sample of individuals with genotypes achieved higher accuracy than only alive individuals with *** linear model,logit model and probit model achieved similar ***:Our conclusion is that genomic prediction of pig survival is feasible in the situation that only alive pigs have genotypes,but genomic information of dead individuals can increase accuracy of genomic prediction by 2.06%to 6.04%.

关键词： Genomic prediction Genotyping strategy Simulation Statistical models Survival

Modulation of Gut Microbiota in Pathological States

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Engineering 2017年第1期3卷 83-89页

作者： Yulan Wang BaohongWang Junfang wu xiangyang Jiang Huiru Tang ole H. nielsen Key Laboratory of Magnetic Resonance in Biological Systems State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics National Center for Magnetic Resonance Wuhan Institute of Physics and Mathematics Chinese Academy of Sciences Wuhan 430071 China National Collaborative Innovation Center for Diagnosis and Treatment of lnfectious Diseases State Key Laboratory for Diagnosis and Treatment of lnfectious Diseases The First Affiliated Hospital School of Medicine Zhejiang University Hangzhou 310003 China State Key Laboratory of Genetic Engineering Zhongshan Hospital and School of Life Sciences Fudan University Collaborative Innovation Center of Genetics and Development Shanghai International Center for Molecular Phenomics Shanghai 200433 China Department of Gastroenterology Medical Section Heriev Hospital University of Copenhagen Copenhagen 1017 Denmark

The human microbiota is an aggregate of microorganisms residing in the human body, mostly in the gastrointestinal tract （GIT）. Our gut microbiota evolves with us and plays a pivotal role in human health and disease. In recent years, the microbiota has gained increasing attention due to its impact on host metabolism, physiology, and immune system development, but also because the perturbation of the microbiota may result in a number of diseases. The gut microbiota may be linked to malignancies such as gastric cancer and colorectal cancer. It may also be linked to disorders such as nonalcoholic fatty liver disease （NAFLD）; obesity and diabetes, which are characterized as ＂lifestyle diseases＂ of the industrial- ized world; coronary heart disease; and neurological disorders. Although the revolution in molecular technologies has provided us with the necessary tools to study the gut microbiota more accurately, we need to elucidate the relationships between the gut microbiota and several human pathologies more precisely, as understanding the impact that the microbiota plays in various diseases is fundamental for the development of novel therapeutic strategies. Therefore, the aim of this review is to provide the read- er with an updated overview of the importance of the gut microbiota for human health and the poten- tial to manipulate gut microbial composition for purposes such as the treatment of antibiotic-resistant Clostridium difficile （C difficile） infections. The concept of altering the gut community by microbial intervention in an effort to improve health is currently in its infancy. However, the therapeutic implications appear to be very great. Thus, the removal of harmful organisms and the enrichment of beneficial mi- crobes may protect our health, and such efforts will pave the way for the development of more rational treatment options in the future.

关键词： Gut microbes Diseases Microbial modulation

Inflammatory pathways of importance for management of inflammatory bowel disease

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World Journal of Gastroenterology 2014年第1期20卷 64-77页

作者： Jannie Pedersen Mehmet Coskun Christoffer Soendergaard Mohammad Salem ole Haagen nielsen Department of Gastroenterology Medical SectionUniversity of CopenhagenHerlev HospitalDK-2730 HerlevDenmark Department of Cellular and Molecular Medicine the Panum InstituteUniversity of CopenhagenDK-2200 CopenhagenDenmark

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.

关键词： Anti-tumor necrosis factor, Biologics, Crohn’ s disease, Pro-inflammatory cytokines, Signaling pathways, Treatment, Ulcerative colitis

Shot-noise limited, supercontinuum-based optical coherence tomography

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Light(Science & Applications) 2021年第7期10卷 1372-1384页

作者： Shreesha Rao D.S. Mikkel Jensen Lars Grüner-nielsen Jesper Toft Olsen Peter Heiduschka björn Kemper Jürgen Schnekenburger Martin Glud Mette Mogensen Niels Møller Israelsen ole Bang DTU Fotonik Dept.of Photonics EngineeringTechnical University of DenmarkØrsteds Plads2800 Kongens LyngbyDenmark NKT Photonics A/S Blokken 843460 BirkerødDenmark Department of Ophthalmology University of Münster Medical CentreDomagkstr.15D-48149 MünsterGermany Biomedical Technology Center of the Medical Faculty University of MünsterMendelstr.17D-48149 MünsterGermany Department of Dermatology Bisbebjerg HospitalUniversity of CopenhagenBispebjerg Bakke 232400 Copenhagen NVDenmark

We present the first demonstration of shot-noise limited supercontinuum-based spectral domain optical coherence tomography(SD-OCT)with an axial resolution of 5.9μm at a center wavelength of 1370 *** supercontinuumbased SD-OCT systems cannot be operated in the shot-noise limited detection regime because of severe pulse-topulse relative intensity noise of the supercontinuum *** overcome this disadvantage,we have developed a low-noise supercontinuum source based on an all-normal dispersion(ANDi)fiber,pumped by a femtosecond *** noise performance of our 90 MHz ANDi fiber-based supercontinuum source is compared to that of two commercial sources operating at 80 and 320 MHz repetition *** show that the low-noise of the ANDi fiber-based supercontinuum source improves the OCT images significantly in terms of both higher contrast,better sensitivity,and improved *** SD-OCT imaging of skin,retina,and multilayer stacks we conclude that supercontinuumbased SD-OCT can enter the domain of shot-noise limited detection.

关键词： fiber optical pumped

Impact of fine particles in ambient air on lung cancer

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Chinese Journal of Cancer 2014年第4期33卷 197-203页

作者： Gerard Hoek ole Raaschou-nielsen Institute for Risk Assessment Sciences Utrecht University Danish Cancer Society Research Center

Recently,the International Agency for Research on Cancer(IARC)has classified outdoor air pollution and the particulate matter component of outdoor air pollution as class I *** pollution is consistently associated with lung cancer in epidemiologic and experimental *** IARC assessment is specifically designed as hazard identification,and it does not quantify the magnitude of the cancer *** article addresses the magnitude of the lung cancer risk in the population due to ambient air pollution exposure.

关键词：环境空气污染肺癌微粒研究机构流行病学危害识别癌症颗粒物

miR-20b, miR-98, miR-125b-1*, and let-7e* as new potential diagnostic biomarkers in ulcerative colitis

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World Journal of Gastroenterology 2013年第27期19卷 4289-4299页

作者： Mehmet Coskun Jacob Tveiten bjerrum Jakob Benedict Seidelin Jesper Thorvald Troelsen JΦrgen Olsen ole Haagen nielsen Department of Gastroenterology Medical SectionHerlev HospitalUniversity of Copenhagen Department of Cellular and Molecular Medicine the Panum InstituteUniversity of Copenhagen Department of Internal Medicine Ⅰ University of CopenhagenBispebjerg Hospital Department of Science Systemsand ModelsRoskilde University

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 *** 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 specifical

关键词： Biomarker Crohn’s disease Diagnostics Inflammatory bowel disease Microarray MicroRNA Ulcerative colitis

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冲绳海槽北部的全新世火山碎屑沉积

海洋科学进展 2007年第1期25卷 34-45页

作者：刘焱光曹东林张德玉孙吉林 nielsen ole bjφerslev 石学法国家海洋局第一海洋研究所玉门油田作业公司甘肃玉门735200 青岛地质勘查开发局山东青岛266071 奥胡斯大学地球科学学院

分析了冲绳海槽北部的CSH1岩芯沉积物中矿物组成、化学元素质量分数和粒度的变化规律，研究结果表明，在全新世期间，日本九州岛发生了2次大规模火山喷发活动，造成大量的火山物质沉积在冲绳海槽北部。从岩芯最上部的沉积物中可识别出2... 详细信息

分析了冲绳海槽北部的CSH1岩芯沉积物中矿物组成、化学元素质量分数和粒度的变化规律，研究结果表明，在全新世期间，日本九州岛发生了2次大规模火山喷发活动，造成大量的火山物质沉积在冲绳海槽北部。从岩芯最上部的沉积物中可识别出2层火山碎屑沉积，它们都具有沉积物粒径突然变粗、SiO2和Na2O等化合物的质量分数突然增加以及粘土矿物、挥发份、Fe2O3、MgO、CaO和Sr的质量分数迅速下降等特征。沉积物粒度数据的端员分析结果表明，冲绳海槽北部全新世沉积物中的硅酸盐碎屑是由陆源碎屑物质和火山灰按不同的比例混合而成的。有火山物质混入的沉积物的粒度分布多呈现双峰模式，粒度众数值分别为74．3和7．81μm。浮游有孔虫壳体的AMS^14C测年结果表明，2层火山碎屑所对应的火山喷发年代分别为7210和***。其中前者与K—Ah火山的喷发时间一致，后者可能与Kuju火山在12～***期间的喷发有关。

关键词：冲绳海槽全新世火山碎屑沉积

MicroRNAs in inflammatory bowel disease-pathogenesis,diagnostics and therapeutics

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World Journal of Gastroenterology 2012年第34期18卷 4629-4634页

作者： Mehmet Coskun Jacob Tveiten bjerrum Jakob Benedict Seidelin ole Haagen nielsen Department of Gastroenterology Medical Section 54 O3University of CopenhagenHerlev HospitalDK-2730 HerlevDenmark Department of Cellular and Molecular Medicine the Panum InstituteUniversity of CopenhagenDK-2200 Copenhagen NDenmark Department of Internal Medicine I University of CopenhagenBispebjerg HospitalDK-2400 Copenhagen NVDenmark

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.

关键词： Biomarker Crohn's disease Diagnostics In-flammatory bowel disease MicroRNA Therapeutics Ulcer-ative colitis