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Osteoarthritis phenotypes and novel therapeutic targets.

July 1, 2019

Biochem Pharmacol

Abstract The success of disease-modifying osteoarthritis drug (DMOAD) development is still elusive. While there have been successes in preclinical and early clinical studies, phase 3 clinical trials have failed so far and there is still no approved, widely available DMOAD on the market. The latest research suggests that, among other causes, poor trial outcomes might […]

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Use of Plasma Fragments of Propeptides of Type III, V, and VI Procollagen for the Detection of Liver Fibrosis in Type 2 Diabetes.

July 1, 2019

Diabetes Care

Abstract OBJECTIVE This study assessed the utility of plasma fragments of propeptides of type III (PRO-C3), V (PRO-C5), and VI (PRO-C6) procollagen for the detection of liver fibrosis in patients with type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODS Patients with T2DM ( = 191) underwent an oral glucose tolerance test, a liver H-MRS, […]

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Bone and Soft Tissue Turnover in Relation to All-cause Mortality in Postmenopausal Women.

June 18, 2019

J Gerontol A Biol Sci Med Sci

Abstract BACKGROUND The relationship between levels of extracellular matrix (ECM) turnover and mortality is currently unknown. The study aimed to determine if levels of ECM turnover are predictors of all-cause mortality in a large cohort of postmenopausal women. METHODS 5,855 postmenopausal Danish women enrolled in the Prospective Epidemiologic Risk Factor (PERF) study. Baseline demographics and […]

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Association of metabolites reflecting type III and VI collagen formation with modified Rodnan skin score in systemic sclerosis – a cross-sectional study.

June 1, 2019

Biomarkers

Abstract The objective was to investigate blood-based biomarkers of type I (PRO-C1), III (PRO-C3) and VI (PRO-C6) collagen formation in systemic sclerosis (SSc) patients and examine their correlation to modified Rodnan skin score (mRSS). Limited (lSSc,  = 76) and diffuse SSc (dSSc,  = 41) fulfilling the ACR/EULAR 1980 and 2013 classification criteria for SSc and asymptomatic controls […]

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Serological Assessment of the Quality of Wound Healing Processes in Crohn’s Disease.

June 1, 2019

J Gastrointestin Liver Dis

Abstract BACKGROUND AND AIMS Crohn’s disease (CD) is a chronic inflammatory condition characterized by continuous mucosal damage and ongoing wound healing of the intestines. The fibrinolytic system is involved in early parts of the wound healing process. Fibrin is a key mediator of primary blood clot formation and is formed by cross-linking of fibrinogen. To […]

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Collagen type IV remodelling gender-specifically predicts mortality in decompensated cirrhosis.

May 1, 2019

Liver Int

Abstract BACKGROUND & AIMS Remodelling of extracellular matrix is crucial in progressive liver fibrosis. Collagen type III desposition has been shown in acute decompensation. Extratracellular matrix is compiled of deposition of various components. The role of basement membrane collagen type IV in advanced cirrhosis and acute decompensation is unclear and investigated in this study. METHODS […]

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Citrullinated vimentin and biglycan protein fingerprints as candidate serological biomarkers for disease activity in systemic sclerosis: a pilot study.

May 1, 2019

Biomarkers

Abstract Extracellular matrix (ECM) deposition and remodelling in skin and lungs of systemic sclerosis (SSc) subjects lead to release of metabolites/biomarkers into circulation. We investigated if biomarkers of ECM degradation (biglycan and elastin) and macrophage activation (citrullinated vimentin) could identify diffuse SSc (dSSc) subjects from controls and the biomarkers discriminative power. DSSc subjects ( = 40) fulfilling […]

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Potential diagnostic value of a type X collagen neo-epitope biomarker for knee osteoarthritis.

April 1, 2019

Osteoarthritis Cartilage

Abstract OBJECTIVE Phenotypic changes of chondrocytes toward hypertrophy might be fundamental in the pathogenesis of osteoarthritis (OA), of which type X collagen (Col10) is a well-known marker. The purpose was to develop a specific immunoassay for blood quantification of a newly identified neo-epitope of type Col10 to assess its diagnostic value for radiographic knee OA. […]

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Type IV collagen turnover is predictive of mortality in COPD: a comparison to fibrinogen in a prospective analysis of the ECLIPSE cohort.

April 1, 2019

Respir Res

Abstract BACKGROUND Identifying subjects with chronic obstructive pulmonary disease (COPD) at high risk of exacerbation and mortality is key to aid individual management of COPD. The only FDA approved blood-based drug development biomarker for patients at high risk of mortality, is plasma fibrinogen. In this study, we benchmarked two biomarkers of basement membrane remodeling, a […]

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Proposed study designs for approval based on a surrogate endpoint and a post-marketing confirmatory study under FDA’s accelerated approval regulations for disease modifying osteoarthritis drugs.

April 1, 2019

Osteoarthritis Cartilage

Abstract In 1992, the Food and Drug Administration (FDA) instituted the accelerated approval regulations that allow drugs or biologics for serious conditions that fill an unmet medical need to be approved on the basis of a surrogate endpoint or an intermediate clinical endpoint. The current definition of a serious condition includes chronic disabling conditions, such […]

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