Publications
Find an abstract and a link to most of the publications produced by Nordic Bioscience
Background Aberrant extracellular matrix (ECM) deposition and remodelling is important in the disease pathogenesis of pulmonary fibrosis (PF). We characterised neoepitope biomarkers released by ECM turnover in lung tissue from bleomycin-treated rats and patients with PF and analysed the effects of ...
August 4, 2022
Journal:
Respiratory Research
Author:
Hesse C, Beneke V, Konzok S, Diefenbach C, Bülow Sand JM, Rønnow S, Karsdal MA, Jonigk D, Sewald K, Braun A, Leeming DJ, Wollin L
Background and aims: Liver fibrosis results from a prolonged wound healing response to continued injury with excessive production of extracellular proteins. In patients with chronic liver disease, the monitoring of liver fibrosis dynamics is of high interest. Whilst markers of fibrogenesis exist, ...
April 12, 2022
Journal:
Liver Int
Author:
Pehrsson M, Manon-Jensen T, Sun S, Villesen IF, Castane H, Joven J, Patel K, Goodman Z, Bay-Jensen AC, Mortensen JH, Karsdal MA, Leeming DJ, Nielsen MJ
Abstract Background: Alcohol is a main cause of preventable deaths and frequently leads to the development of alcohol-related liver disease. Due to the lack of diagnostics, patients are commonly diagnosed after developing clinical manifestations. Recently, the biomarker PRO-C3 was shown to accura...
September 5, 2021
Journal:
Aliment Pharmacol Ther.
Author:
Madsen BS, Thiele M, Detlefsen S, Kjaergaard M, Møller LS, Gudmann Stæhr N, Leeming DJ, Krag A, Nielsen MJ, Trebicka JK
Background & aims: Non-alcoholic fatty liver disease (NAFLD) is a common liver disorder with non-alcoholic steatohepatitis (NASH) being a more progressive phenotype associated with progression to cirrhosis. Type III collagen is a main component of the fibrotic extracellular matrix. PRO-C3 is a b...
August 26, 2021
Journal:
J Hepatol
Author:
Leeming DJ, Goodman Z, Friedman S, Frederiksen P, Vig P, Seyedkazemi S, Fischer L, Torstenson R, Karsdal MA, Lefebvre E, Sanyal JA, Ratziu V, Nielsen MJ
Objectives: There is a need for precision medicine and an unspoken promise of an optimal approach for identification of the right patients for value-based medicine based on big data. However, there may be a misconception that measurement of proteins is more valuable than measurement of fewer selecte...
August 26, 2021
Journal:
Clin Biochem
Author:
Karsdal MA, Rasmussen DGK, Bay-Jensen AC, Mortensen JH, Holm Nielsen S, Willumsen N, Jensen C, Manon-Jensen T, Jennings L, Reese-Petersen AL, Henriksen K, Leeming DJ, Bager CL, Genovese F, Bülow Sand JM
Background: Liver fibrosis accumulation is considered a turnover disease, with formation exceeding degradation, although this hypothesis has never been tested in humans. Aims: To investigate extracellular matrix (ECM) remodelling in a biopsy-controlled study of alcohol-related liver disease (ALD) p...
August 24, 2021
Journal:
Aliment Pharmacol Ther.
Author:
Thiele M, Johansen S, Gudmann NS, Kjaergaard M, Leeming DJ, Jacobsen S, Bendtsen F, Møller S, Detlefsen S, Karsdal MA, Krag A, Madsen BS, Nielsen MJ
Abstract Background: Asthma is a heterogeneous syndrome substantiating the urgent requirement for endotype-specific biomarkers. Dysbalance of fibrosis and fibrolysis in asthmatic lung tissue leads to reduced levels of the inflammation-protective collagen 4 (COL4A3). Objective: To delineate the degra...
July 29, 2021
Journal:
Eur Respir J
Author:
Weckmann M, Bahmer T, Rønnow S, Pech M, Vermeulen C, Faiz A, Karsdal MA, Lunding L, Oliver B, Wegmann M, Ulrich-Merzenich G, Juergens U, Duhn J, Laumonnier Y, Danov O, Sewald K, Zissler U, Jonker M, König I, Hansen G, Mutius E, Fuchs O, Dittrich AM, Schaub B, Happle C, Rabe K, de Berge M, Burgess J, Kopp M, Leeming DJ, Bülow Sand JM
Abstract Background: Idiopathic pulmonary fibrosis (IPF) is characterized by the accumulation of fibrillar collagens in the alveolar space resulting in reduced pulmonary function and a high mortality rate. Biomarkers measuring the turnover of type I and III collagen could provide valuable informa...
July 15, 2021
Journal:
Respir Res.
Author:
Leeming DJ, Jessen H, Hoyer N, Prior TS, Frederiksen P, Karsdal MA, Bendstrup E, Bülow Sand JM, Shaker SB
Background & aims: Progressive fibrosis has been identified as the major predictor of mortality in patients with non-alcoholic fatty liver disease (NAFLD). Several biomarkers are currently being evaluated for their ability to substitute the liver biopsy as the reference standard. Recent clinical...
July 10, 2021
Journal:
JHEP Rep
Author:
Erhardtsen E, Rasmussen DGK, Frederiksen P, Leeming DJ, Gluud LL, Karsdal MA, Aithal GP, Shattenberg JM, Shevell DE
Background: Rupture of atherosclerotic plaques is the major cause of acute cardiovascular events. The biomarker PRO-C6 measuring Endotrophin, a matrikine of collagen type VI, may provide valuable information detecting subjects in need of intensified strategies for secondary prevention. Objective: I...
May 5, 2021
Journal:
J Intern Med
Author:
Holm Nielsen S, Edsfeldt A, Tengryd C, Gustafsson H, Shore CA, Natali A, Khan F, Bengtsson E, Karsdal MA, Leeming DJ, Nilsson J, Goncalves I, Genovese F
Background and objective: Prediction of idiopathic pulmonary fibrosis (IPF) progression is vital for the choice and timing of treatment and patient follow-up. This could potentially be achieved by prognostic blood biomarkers of extracellular matrix (ECM) remodelling. Methods: Neoepitope biomarkers ...
April 9, 2021
Journal:
Respirology
Author:
Hoyer N, H Jessen, Leeming DJ, Karsdal MA, Åttingsberg KAE, Vangsgaard KMG, Bendstrup E, Shaker SB, Prior TS, Bülow Sand JM
Pulmonary fibrosis has been identified as a main factor leading to pulmonary dysfunction and poor quality of life in post-recovery Severe Acute Respiratory Syndrome (SARS) survivor's consequent to SARS-Cov-2 infection. Thus there is an urgent medical need for identification of readily available biom...
February 5, 2021
Journal:
Respir Res.
Author:
Leeming DJ, Rasmussen DGK, Christiansen C, Jenkins G, Mahrer TM, Vestbo J, Karsdal MA, Genovese F, Bülow Sand JM
Aim: Type VI collagen, is emerging as a signaling collagen originating from different types of fibroblasts. A specific fragment of Type VI collagen, the pro-peptide, is also known as the hormone endotrophin. We hypothesized that this fibroblast hormone would be of particular relevance in cancer ty...
December 18, 2020
Journal:
Hepatic Oncology
Author:
Holm Nielsen S, Vongsuvanh R, Uchila R, Reese-Petersen AL, van der Poorten D, Eslam M, Schuppan D, George J, Leeming DJ, Karsdal MA, Nielsen MJ
Introduction: Metabolic-associated fatty liver disease is common, with fibrosis the major determinant of adverse outcomes. Population-based screening tools with high diagnostic accuracy for the staging of fibrosis are lacking. Methods: Three independent cohorts, 2 with both liver biopsy and liver s...
November 26, 2020
Journal:
Am J Physiol Gastrointest Liver Physiol
Author:
Eslam M, Wong GL, Hashem AM, Chan HL, Nielsen MJ, Leeming DJ, Chan AW, Chen Y, Duffin KL, Schattenberg JM, George J, Wong VW, Karsdal MA
New therapeutic strategies are needed for the growing unmet clinical needs in liver disease and fibrosis. Platelet activation and PDGF activity are recognized as important therapeutic targets; however, no therapeutic approach has yet addressed these two upstream drivers of liver fibrosis. We therefo...
November 20, 2020
Journal:
Biomaterials
Author:
Kabra H, Walimbe T, Stuart K, Indey C, Jalgaonkar S, Ikwa E, Skurnac T, Chen J, Woolley A, Snead NM, Bachtell N, Leeming DJ, Prestwich G, Panitch A, Paderi J, Karsdal MA
Purpose: Non-invasive biomarkers for diagnosing and prognosing hepatocellular carcinoma (HCC) are urgently needed. Cirrhosis is present in 80-90% of HCC patients. Cirrhosis is characterized by deposition and cross-linking of collagens that have crucial roles in HCC initiation and progression. We eva...
November 20, 2020
Journal:
J Hepatocell Carcinoma
Author:
Jensen C, Holm Nielsen S, Eslam M, Genovese F, Nielsen MJ, Vongsuvanh R, Uchila R, van der Poorten D, George J, Karsdal MA, Leeming DJ, Willumsen N.
Background: Chronic obstructive pulmonary disease (COPD) is characterized by abnormal epithelial repair resulting in a hypercoagulable state with intra-alveolar accumulation of fibrin and alveolar basement membrane destruction. This study aimed to investigate if the combination of two serological bi...
November 19, 2020
Journal:
Lancet Respir Med
Author:
Langholm LL, Karsdal MA, Manon-Jensen T, Miller BE, Vestbo J, Leeming DJ, Thal-Singer R, Bülow Sand JM, Rønnow S
The effect of direct-acting antiviral (DAA) therapy on extracellular matrix (ECM) turnover, a prominent feature of chronic hepatitis C (CHC), is unknown. ECM protein degradation and formation generate fragments reflecting the tissue turnover balance when quantified in the blood. PRO-C3 and PRO-C4 re...
October 15, 2020
Journal:
J Viral Hepat
Author:
Laursen TL, Villesen IF, Leeming DJ, Karsdal MA, Sølund C, Tarp B, Kristensen LH, Holmboe CH, Leuthcher P, Laursen AL, Gudmann NS, Grønbaek H
Background & aims: Primary sclerosing cholangitis (PSC), primary biliary cholangitis (PBC) and autoimmune hepatitis (AIH) are phenotypically distinct autoimmune liver diseases that progress to cirrhosis and liver failure; however, their histological fibrosis distribution differs. We investigated...
September 3, 2020
Journal:
JHEP Rep
Author:
Vesterhus M, Nielsen MJ, Hov JR, Saffioti F, Manon-Jensen T, Leeming DJ, Moum B, Boberg KM, Pinzani M, Karlsen TH, Karsdal MA, Thorburn D
Background: Lung epithelial damage, activation of the wound healing cascade, and remodeling of the extracellular matrix (ECM) play a major role in chronic obstructive pulmonary disease (COPD). The pro-peptide of type VI collagen has been identified as the hormone endotrophin. Endotrophin has been sh...
July 30, 2020
Journal:
Respir Res.
Author:
Rønnow S, Langholm LL, Karsdal MA, Manon-Jensen T, Miller BE, Vestbo J, Leeming DJ, Bülow Sand JM, Thal-Singer R
There is an unmet need for high-quality liquid biomarkers that can safely and reproducibly predict the stage of fibrosis and the outcomes of chronic liver disease (CLD). The requirement for such markers has intensified because of the high global prevalence of diseases such as non-alcoholic fatty liv...
April 9, 2020
Journal:
Liver Int
Author:
Karsdal MA, Daniels SJ, Nielsen SH, Bager CL, Rasmussen DGK, Loomba R, Surabattula R, Villesen IF, Luo Y, Gudmann NS, Nielsen MJ, George J, Christian R, Leeming DJ, Schuppan D, Shevell DE
Extracellular matrix (ECM) remodeling is a hallmark of the pathology of gastrointestinal disorders. Collagen type VI (COL6) is produced by fibroblasts, and the COL6 α3-chain has shown to be elevated in patients with ulcerative colitis (UC), Crohn's disease (CD) and colorectal cancer (CRC). Measuring...
April 3, 2020
Journal:
Sci Rep
Author:
Nielsen SH, Mortensen JH, Willumsen N, Mogensen DJ, Di Sabatino A, Mazza G, Jørgensen LN, Pinzani M, Klinge LG, Kjeldsen J, Leeming DJ, Karsdal MA, Genovese F, Rasmussen DGK, Giuffrida P
Chronic obstructive pulmonary disease (COPD) is characterized by a slow heterogeneous progression. Therefore, improved biomarkers that can accurately identify patients with the highest likelihood of progression and therefore the ability to benefit from a given treatment, are needed. Elastin is an es...
March 11, 2020
Journal:
Sci Rep
Author:
Rønnow S, Langholm LL, Leeming DJ, Manon-Jensen T, Miller BE, Karsdal MA, Vestbo J, Thal-Singer R, Thoracius-Ussing J, Bülow Sand JM
Background: Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation and lung tissue deterioration. Given the high vascularity of the lung, von Willebrand factor (VWF), a central component of wound healing initiation, has previously been assessed in COPD. VWF processing,...
March 9, 2020
Journal:
Int J Chron Obstruct Pulmon
Author:
Langholm LL, Rønnow S, Leeming DJ, Miller BE, Vestbo J, Karsdal MA, Manon-Jensen T, Bülow Sand JM, Thal-Singer R
Nonalcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD) are common causes of chronic liver disease. The overlap between ALD and NAFLD suggests the existence of metabolic steatohepatitis. Development of in vivo models that reflect various aspects of human steatohepatitis is essenti...
January 6, 2020
Journal:
Am J Physiol Gastrointest Liver Physiol
Author:
Daniels SJ, Leeming DJ, Detlefsen S, Bruun MF, Hjuler ST, Henriksen K, Hein P, Krag A, Karsdal MA, Nielsen MJ, Brockbank S, Cruwys S
An altered liver microenvironment characterized by a dysregulated extracellular matrix (ECM) supports the development and progression of hepatocellular carcinoma (HCC). The development of experimental platforms able to reproduce these physio-pathological conditions is essential in order to identify ...
December 28, 2019
Journal:
Cells
Author:
Mazza G, Telese A, Al-Akkad W, Frenguelli L, Levi A, Marrali M, Longato L, Thanapirom K, Vilia MG, Lombardi B, Crowley C, Crawford M, Karsdal MA, Leeming DJ, Marrone G, Bottcher K, Robinson B, Del Rio Hernandez A, Tamburrino D, Spoletini G, Malago M, Hall AR, Godovac-Zimmermann J, Luong TV, De Coppi P, Pinzani M, Rombouts K
Background: Chronic obstructive pulmonary disease (COPD) is characterized by abnormal epithelial repair process that may result in intra-airway accumulation of fibrin. Given that plasma fibrinogen is the only FDA approved biomarker that predicts mortality and COPD exacerbations, we hypothesized that...
December 2, 2019
Journal:
Lancet Respir Med
Author:
Manon-Jensen T, Langholm LL, Karsdal MA, Vestbo J, Leeming DJ, Miller BE, Thal-Singer R, Bülow Sand JM, Rønnow S
Therapies to reduce liver fibrosis and stimulate organ regeneration are urgently needed. We conducted a first-in-human, phase 1 dose-escalation trial of autologous macrophage therapy in nine adults with cirrhosis and a Model for End-Stage Liver Disease (MELD) score of 10-16 (ISRCTN 10368050). Groups...
October 25, 2019
Journal:
Nat Med
Author:
Moroni F, Dwyer BJ, Graham C, Pass C, Bailey L, Ritchie L, Mitchell D, Glover A, Lauire A, Doig S, Hargreaves E, Fraser AR, Turner ML, Cambpell JDM, McGowan NWA, Barry J, Moore JK, Hayes PC, Leeming DJ, Nielsen MJ, Musa K, Fallowfield JA, Forbes SJ
BACKGROUND: Lifestyle modifications remain the cornerstone of treatment in non-alcoholic fatty liver disease (NAFLD). However, they requently fail related to the inability of patients to implement lasting changes. AIMS: To evaluate the effects of a short, web-based, individualised exercise program ...
October 16, 2019
Journal:
Aliment Pharmacol Ther.
Author:
Huber Y, Pfirrmann D, Gebhardt I, Labenz C, Gehrke N, Straub C, Ruckes C, Bantel H, Belda E, Clément K, Leeming DJ, Karsdal MA, Galle PR, Simon P, Schattenberg JM
Following liver transplantation (LT), 10-30% of patients develop recurrent cirrhosis (RC). There is an urgent need for predictive non-invasive markers for improved monitoring of these patients. Here we studied extracellular matrix biomarkers as predictors of RC after LT. Forty-seven LT patients were...
October 16, 2019
Journal:
Sci Rep
Author:
Nielsen MJ, Villesen IF, Gudmann NS, Leeming DJ, Krag A, Karsdal MA, Zimmermann T, Schuppan D
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