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Peginterferon Lambda-1a, a New Therapeutic for Hepatitis C Infection, from Bench to Clinic

Journal of Clinical and Translational Hepatology 2013年第2期1卷 116-124页

作者： henrik andersen Jeff Meyer Jeremy Freeman Sean E.Doyle Kevin Klucher Dennis M.Miller Diana Hausman Jan L.Hillson ZymoGenetics/Bristol-Myers Squibb Seattle WA 98102 USA EMD Serono Billerica MA USA Oncothyreon Inc. Seattle WA USA CPTxBio Woodinville WA USA

Chronic infection with hepatitis C virus (HCV) is estimated to affect approximately 3% of the world's population and cause 350,000 deaths each *** number of years,the standard of care has been combination therapy with recombinant alfa interferons—originally as native proteins but more recently as polyethyleneglycol-modified derivatives—and ribavirin,with the recent addition of an NS3 protease inhibitor for HCV genotype ***,therapeutic alfa interferons are associated with a significant burden of treatment-limiting adverse events,including musculoskeletal and influenza-like symptoms,hematologic cytopenias,autoimmune disease,fatigue,and other neurologic *** 2003,a team at ZymoGenetics (now a fully owned subsidiary of Bristol-Myers Squibb) and a second,independent group simultaneously identified a new class of interferons—the type Ⅲ lambda interferons—with near-identical activity to the type Ⅰ alfa interferons in hepatocytes but with an unrelated and less ubiquitous *** evaluation of the type Ⅲ interferon system demonstrated antiviral activity against HCV in vitro with limited activity in peripheral blood mononuclear cells and other nonhepatocyte cell types,supporting its development as a potentially better-tolerated therapy for viral *** lambda-1a (Lambda) is an investigational type Ⅲ therapeutic agent originally developed at ZymoGenetics that is currently in Phase 3 studies for the treatment of *** this review,we describe the selection of the Lambda molecule and its preclinical and early clinical development,and how the resulting data have helped to establish the differentiated safety profile for Lambda—with fewer influenza-like and musculoskeletal symptoms and less hematologic toxicity than the alfa interferons—that was seen in later studies.

关键词： Discovery HCV Interferonλ

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Retinal Vessels Diameter Changes during Pregnancy in Type 1 Diabetes

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Open Journal of Ophthalmology 2013年第2期3卷 27-32页

作者： Aurore Mensah Afrouz Ahmadzadeh Ann-Sofie Svanbom Lene Ringholm Birgit Sander henrik Lund-andersen Elisabeth Mathiesen Michael Larsen Department of Endocrinology Rigshospitalet Copenhagen Denmark Department of Ophthalmology Glostrup Hospital Glostrup Denmark Faculty of Health Sciences University of Copenhagen Copenhagen Denmark

Objective: Investigate how pregnancy-induced hormonal and hemodynamic changes affect retinal vessels caliber dynamic and the course of diabetic retinopathy. Methods: Retinopathy grading and vessel diameter measurement using digital fundus photographs in women with diabetes type 1 taken no more than one year before conception, during week 10 and/or 22, week 34, and within one year after delivery. Calibers were measured using a custom-developed semi-automated computer algorithm which identified the six largest arteries and six largest veins and calculated the central retinal artery equivalent (CRAE) and central vein equivalent (CRVE) diameters. Glycemic control was assessed quarterly by HbA1c. Systolic and diastolic blood pressure was assessed at week 10, 22 and 34. Results: Photographs at baseline, weeks 10, 22, 34 and after delivery were available in 28 patients, of whom 24 did not progress in retinopathy. For those whose level of retinopathy remained stable CRAE constricted from 138.80 ± 21.27 μm at baseline to 129.88 ± 13.97 μm at week 10 (p = 0.0379) CRVE constricted from 195.16 ± 24.98 μm at baseline to 185.97 ± 21.96 μm at week 10 (p = 0.0400). The patients with retinopathy progression had a CRAE of 131.67 ± 13.37 μm at baseline and 132.08 ± 11.07 μm at week 10 (p = 0.34) while CRVE was 195.33 ± 24.92 μm at baseline and 204.27 ± 10.18 μm at week 10 (p = 0.16). Progressors had higher blood pressures at week 10. Conclusion: Retinal vessels constricted between prepregnancy and first trimester in women who did not experience diabetic retinopathy progression. The study suggests that the vessels constriction seen in early pregnancy contributes to reduce the risk of gestational microvascular complications and progression of diabetes in the eye.

关键词： Pregnancy and Diabetes Type 1 Diabetic Retinopathy Central Retinal Artery Equivalent Central Retinal Vein Equivalent.

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Extracellular Vesicles from Mesenchymal Stromal Cells (imEVs) Improve Cold Preservation of Isolated Mitochondria

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Journal of Biosciences and Medicines 2024年第1期12卷 52-63页

作者： Xianpeng Jiang Sergey Rodin Ken Braesch-andersen Catherine C. Baucom Karl-henrik Grinnemo Brent Segal Elliott Mitochondrial Center Sallie Astor Burdine Breast Foundation Baton Rouge Louisiana USA Mitosense Inc. Boston Massachusetts USA Department of Surgical Sciences Division of Cardiothoracic Surgery Cardio-Thoracic Translational Medicine (CTTM) Laboratory Uppsala University Uppsala University Hospital Uppsala Sweden

Mitochondrial organelle transplantation (MOT) is an innovative strategy for the treatment of mitochondrial dysfunction such as cardiac ischemic reperfusion injuries, Parkinson’s diseases, brain and spinal cord injuries, and amyotrophic lateral sclerosis (ALS). However, one of the major challenges for widespread usage is a methodology for preservation of isolated mitochondria. Extracellular vesicles (EVs) are phospholipid bilayer-enclosed vesicles released from cells. EVs carry a cargo of proteins, nucleic acids, lipids, metabolites, and even organelles such as mitochondria. Purpose: To test if EVs enhance the stability of isolated mitochondria. Methods: We mixed isolated mitochondria of fibroblasts with EVs of mesenchymal stromal cells (imEVs) (9:1 in volume) and stored the mixture at 2°C - 6°C for different time periods. We measured morphology, mitochondrial membrane potential (MMP) and mitochondrial ATP content at 0, 2, 5 days. Key findings: After 2 days of storage, the mito-chondria without imEVs lost approximate 70% MMP (RFU: 1822 ± 68), compared to the fresh mitochondria (RFU: 5458 ± 52) (p 0.05). In agreement with MMP, mitochondria without imEVs lost significant mitochondrial ATP content (p 0.05), after 2 days of cold storage, compared to fresh mitochondria. Microscopy showed that imEVs promoted aggregation of isolated mitochondria. Summary: The preliminary data showed that imEVs enhanced the stability of isolated mitochondria in cold storage.

关键词： Mitochondria Extracellular Vesicles Mitochondrial Preservation MOT imEVs

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Oxidation controlled lift-off of 3D chiral plasmonic Au nano-hooks

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Nano Research 2019年第7期12卷 1635-1642页

作者： Gunnar Klos Amanda andersen Matteo Miola henrik Birkedal Duncan S. Sutherland Interdisciplinary Nanoscience Center (iNANO) Aarhus UniversityAarhus C 8000Denmark Department of Chemistry and iNANO Aarhus UniversityAarhus C 8000Denmark Carbon Dioxide Activation Center (CADIAC)- iNANO Aarhus UniversityAarhus C 8000Denmark

Colloidal suspensions of plasmonic nanoparticles (NPs) are a well-established tool for biomedical applications and enhanced spectroscopy because of their strong optical *** specific response is greatly dependent on the NP *** strong optical activity of chiral NPs has created special interest but fabrication of chiral NPs in solution remains ***,we present an approach whereby three-dimensional (3D) chiral Au nano-hooks,fabricated with the parallel hole-mask colloidal lithography (HMCL) method,can be lifted off from a glass substrate in a controllable manner by using a combined treatment with oxygen plasma oxidation and a reduction step in *** method has the advantage of being based on established techniques and not requiring strong acids or complex substrates as in etching based *** furthermore demonstrate the integration of the hook NPs into reversibly cross-linked hydrogels inspired by mussel catechol chemistry but containing an oxidation resistant catechol analogue grafted onto poly(allylamine) crosslinked by coordination of Al^3+ and how this facilitates the remote analysis of hydrogel microenvironment,*** water *** suspended particles are promising candidates for optically active surface-enhanced Raman spectroscopy (SERS),asymmetric photo catalysis or aggregation *** integration into hydrogels to produce functional hydrogels holds benefits for applications of metamaterials in optics,sensing or activation in environmental remediation or drug delivery.

关键词： chiral nanostructures circular dichroism plasmonic sensor hole-mask colloidal lithography

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An arctic low-energy house as experimental setup for studies of heat dynamics of buildings

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Frontiers of Architectural Research 2013年第4期2卷 488-499页

作者： Philip Delft andersen Carsten Rode henrik Madsen DTU Compute Richard Pedersens Plads Technical University of Denmark Building 322 Kongens Lyngyb DK-2800 Denmark DTU Civil Engineering Brovej Bygning 118 Technical University of Denmark Kongens Lyngyb DK-2800 Denmark

This paper addresses the difficulties in pinpointing reasons for unexpectedly high energy consumption in construction, and in low-energy houses especially. Statistical methods are applied to improve the insight into the energy performance and heat dynamics of a building based on consumption records and weather data. Dynamical methods separate influences from outdoor temperature, solar radiation, and wind on the energy consumption in the building. The studied building is a low-energy house in Sisimiut, GreenLand. Weather conditions like large temperature differences between indoors and outdoors throughout tong winters, strong winds, and very different circumstances regarding solar radiation compared to areas where Low-energy houses are usually built, make the Location very interesting for modeling and testing purposes. In 2011 new measurement equipment was installed in the house, which will be used to develop more detailed models of the heat dynamics and energy performance in relation to different meteoroLogicaL variables, heating systems, and user behavior. This type of models is known as a graybox model and is been introduced in this paper.

关键词： Low-energy houses Heat dynamics Arctic climate Statistical modeling Graybox modeling

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First attempt to produce experimental Campylobacter concisus infection in mice

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World Journal of Gastroenterology 2008年第45期14卷 6954-6959页

作者： Rune Aabenhus Unne Stenram Leif Percival andersen henrik Permin sa Ljungh Department of Clinical Microbiology National University Hospital (Rigshospitalet) Department of Pathology University of Lund Department of Infectious Control and Prevention National University Hospital (Rigshospitalet) Department of Internal Medicine Bispebjerg Hospital Department of Medical Microbiology Dermatology and Infection Lund University

AIM： TO infect mice with atypical Campylobacter concisus （C. concisus） for the first time. METHODS： Three separate experiments were conducted in order to screen the ability of five clinical C. concisus isolates of intestinal origin and the ATCC 33237 type strain of oral origin to colonize and produce infection in immunocompetent BALB/cA mice. The majority of the BALB/cA mice were treated with cyclophosphamide prior to C. concisus inoculation to suppress immune functions. Inoculation of C. conc/sus was performed by the gastric route. RESULTS： C. concisus was isolated from the liver, ileum and jejunum of cyclophosphamide-treated mice in the first experiment. No C. concisus strains were isolated in the two subsequent experiments. Mice infected with C. concisus showed a significant loss of body weight from day two through to day five of infection but this decreased at the end of the first week. Histopathological examination did not consistently find signs of inflammation in the gut, but occasionally microabscesses were found in the liver of infected animals. CONCLUSION： Transient colonization with C. concisus was observed in mice with loss of body weight. Future studies should concentrate on the first few days after inoculation and in other strains of mice.

关键词： Animal model BALB/cA mice Campylobacter concisus Colonization Infection

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Polymorphisms in NF-κB,PXR,LXR,PPARγ and risk of inflammatory bowel disease

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World Journal of Gastroenterology 2011年第2期17卷 197-206页

作者： Vibeke andersen Jane Christensen Anja Ernst Bent A Jacobsen Anne Tjφnneland henrik B Krarup Ulla Vogel Department of Medical Viborg Regional Hospital Institute of Cancer Epidemiology Danish Cancer Society Department of Clinical Biochemistry Aarhus University Hospital Department of Medical Gastroenterology Aarhus University Hospital National Food Institute Technical University of Denmark Institute for Science Systems and ModelsUniversity of Roskilde National Research Centre for the Working Environment

AIM:To investigate the contribution of polymorphisms in nuclear receptors to risk of inflammatory bowel disease(IBD) . METHODS:Genotypes of nuclear factor(NF) -κB(NFKB1) NFκB-94ins/del(rs28362491) ;peroxisome proliferatoractivated receptor(PPAR) -γ(PPARγ) PPARγPro12Ala(rs1801282) and C1431T(rs 3856806) ;pregnane X receptor(PXR) (NR1I2) PXR A-24381C(rs1523127) ,C8055T(2276707) ,and A7635G(rs 6785049) ;and liver X receptor(LXR) (NR1H2) LXR T-rs1405655-C and T-rs2695121-C were assessed in a Danish case-control study of 327 Crohn's disease patients,495 ulcerative colitis(UC) patients,and 779 healthy *** ratio(OR) and 95%CI were estimated by logistic regression models. RESULTS:The PXR A7635G variant,the PPARγPro12Ala and LXR T-rs2695121-C homozygous variant genotypes were associated with risk of UC(OR:1.31,95% CI:1.03-1.66,P=0.03,OR:2.30,95%CI:1.04-5.08,P=0.04,and OR:1.41,95%CI:1.00-1.98,P=0.05,respectively) compared to the corresponding homozygous wild-type *** never smokers,PXR A7635G and the LXR T-rs1405655-C and T-rs2695121-C variant genotypes were associated with risk of IBD(OR:1.41,95%CI:1.05-1.91,P=0.02,OR:1.63,95%CI:1.21-2.20,P=0.001,and OR:2.02,95%CI:1.36-2.99,P=0.0005,respectively) compared to the respective homozygous variant *** A7635G(rs6785049) variant genotype was associated with a higher risk of UC diagnosis before the age of 40 years and with a higher risk of extensive disease(OR:1.34,95%CI:1.03-1.75 and OR:2.49,95%CI:1.24-5.03,respectively) . CONCLUSION:Common PXR and LXR polymorphisms may contribute to risk of IBD,especially among never smokers.

关键词： Crohn's disease Genetic susceptibility Single nucleotide polymorphisms Smoking status Transcription factors Ulcerative colitis

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Low-FODMAP diet reduces irritable bowel symptoms in patients with inflammatory bowel disease

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World Journal of Gastroenterology 2017年第18期23卷 3356-3366页

作者： Natalia Pedersen Dorit Vedel Ankersen Maria Felding henrik Wachmann Zsuzsanna Végh Line Molzen Johan Burisch Jens Rikardt andersen Pia Munkholm Department of Gastroenterology Slagelse Hospital Gastroenterology Unit North Zealand Hospital Department of Nutrition Exercise and SportsUniversity of Copenhagen Department of Statistics First Department of Medicine Semmelweis University

To investigate the effect of a low-FODMAP diet on irritable bowel syndrome (IBS)-like symptoms in patients with inflammatory bowel disease (IBD).METHODSThis was a randomised controlled open-label trial of patients with IBD in remission or with mild-to-moderate disease and coexisting IBS-like symptoms (Rome III) randomly assigned to a Low-FODMAP diet (LFD) or a normal diet (ND) for 6 wk between June 2012 and December 2013. Patients completed the IBS symptom severity system (IBS-SSS) and short IBD quality of life questionnaire (SIBDQ) at weeks 0 and 6. The primary end-point was response rates (at least 50-point reduction) in IBS-SSS at week 6 between groups; secondary end-point was the impact on quality of ***-nine patients, 67 (75%) women, median age 40, range 20-70 years were randomised: 44 to LFD group and 45 to ND, from which 78 patients completed the study period and were included in the final analysis (37 LFD and 41 ND). There was a significantly larger proportion of responders in the LFD group (n = 30, 81%) than in the ND group (n = 19, 46%); (OR = 5.30; 95%CI: 1.81-15.55, P < 0.01). At week 6, the LFD group showed a significantly lower median IBS-SSS (median 115; inter-quartile range [IQR] 33-169) than ND group (median 170, IQR 91-288), P = 0.02. Furthermore, the LFD group had a significantly greater increase in SIBDQ (median 60, IQR 51-65) than the ND group (median 50, IQR 39-60), P < *** a prospective study, a low-FODMAP diet reduced IBS-like symptoms and increased quality of life in patients with IBD in remission.

关键词： Inflammatory bowel disease Web-based management Irritable bowel syndrome Low-FODMAP diet

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Hepatitis B among Inuit: A review with focus on Greenland Inuit

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World Journal of Hepatology 2015年第9期7卷 1265-1271页

作者： Karsten Fleischer Rex Stig andersen henrik Bygum Krarup Department of Internal Medicine Queen Ingrid’s Hospital Arctic Health Research Centre Clinical Institute Aalborg University Hospital Greenland Centre for Health Research Institute of Nursing and Health Science University of Greenland Department of Geriatric and Internal Medicine Aalborg University Hospital Section of Molecular Diagnostics Clinical Biochemistry Aalborg University Hospital

Hepatitis B virus(HBV) infection is a disease with a highly variable course. Chronic HBV infection may cause end-stage liver disease including cirrhosis and hepatocellular carcinoma, which is the 3rd most common cause of cancer related death due to the poor prognosis. The prevalence of HBV infection is low in many countries. Still, it remains important due to the potential consequences of the disease. HBV is endemic in the Arctic with serologic markers of chronic HBV infection in up to 29% of the population in some areas in Greenland. Interestingly, Inuit populations rarely show signs of liver disease despite the fact that around half of all Inuit has been exposed to HBV and around 8% of Inuit are chronically infected with HBV. These findings have been consistent in surveys conducted for more than four decades among Arctic Inuit. We thus review HBV infection in the Arctic with focus on Greenland Inuit and compared with Inuit in Canada, Alaska and Siberia. The aspects described include epidemiology and monitoring of the disease, as well as treatment and the risk of liver cancer.

关键词： Hepatitis B Hepatitis D Monitoring disease Prevention Liver cancer Inuit Greenland Arctic

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Effect of Gastrointestinal Protease Digestion on Bioactivity of Marine Peptides

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Journal of Agricultural Science and Technology(B) 2014年第1期4卷 74-84页

作者： Ida-Johanne Jensen Lisa Lystbek andersen Carlo Gunnar Ossum Greta Jakobsen Cristian De Gobba Sabeena Farvin Koduvayur Habeebullah Inez Johansson Else Hoffmann Edel Oddny Elvevoll Flemming Jessen henrik Hauch Nielsen Faculty of Bioscience Fisheries and Economics Norwegian College of FisheO Science UniversiO of Tromso Tromso 9037Norway Division ofIndustrial Food Research National Food Institute DTU-Food Technical University qf Denmark Lyngby DK-2800Denmark Department of Biology Cell and Developmental Biology Universitv of Copenhagen Copenhagen 2100 Denmark Marinova ApS Adelvej 11 Lem St. 6940 Denmark Department of Food Science University o[Copenhagen Frederiksberg C 1958 Denmark

Focus in nutritional science has turned towards components in, or added to, foods that may possess health beneficial activities beyond the classical nutritional value, namely functional food. Bioactive peptides are examples of such components. In vitro studies on bioactivities have mainly been executed without concerning subsequent digestion after intake and the aim of this work was hence to investigate how the in vitro antioxidative, antihypertensive and caspase activating activities of peptides are affected by digestion with gastrointestinal （GI） proteases. Five different fish protein hydrolysates were chosen to study the effect of in vitro digestion on bioactivity. The protein concentration decreased in all samples during digestion and the molecular weight distribution of the peptides shifted towards lower values. Thus, in vitro digestion with GI proteases resulted in a further degradation of the peptides obtained by hydrolysis. The antihypertensive effect increased in all samples after digestion with GI proteases whereas the antioxidative capacity decreased. The effect on the caspase activity depended on the proteases used in the preparation of hydrolysates. In conclusion, the caspase activity and antihypertensive activity are maintained during digestion with GI proteases, while the antioxidative capacity seems to be reduced.

关键词： Antioxidative ACE in vitro caspase bioactivity marine peptides.

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