53 Publication(s) found
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Cardiovascular System, Extracellular Matrix Research
14. Dec 2017

Understanding Cardiac Extracellular Matrix Remodeling to Develop Biomarkers of Myocardial Infarction Outcomes

Cardiovascular Disease (CVD) is the most common cause of death in industrialized countries, and myocardial infarction (MI) is a major CVD with significant morbidity and mortality. Following MI, the left ventricle (LV) undergoes a wound healing response to ischemia that results in extracellular matri…

Rheumatology, Osteoarthritis
12. Dec 2017

Sprifermin (rhFGF18) Modulates Extracellular Matrix Turnover in Cartilage Explants ex vivo

BACKGROUND:
Sprifermin (recombinant human fibroblast growth factor 18) is in clinical development as a potential disease-modifying osteoarthritis drug (DMOAD). In vitro studies have shown that cartilage regenerative properties of sprifermin involve chondrocyte proliferation and extracellular matrix…

Renal System, Chronic Renal Disease
11. Dec 2017

Urinary endotrophin predicts disease progression in patients with chronic kidney disease

Renal fibrosis is the central pathogenic process in progression of chronic kidney disease (CKD). Collagen type VI (COL VI) is upregulated in renal fibrosis. Endotrophin is released from COL VI and promotes pleiotropic pro-fibrotic effects. Kidney disease severity varies considerably and accurate inf…

Chronic Obstructive Pulmonary Disease, Respiratory System
4. Dec 2017

Biomarkers of collagen turnover are related to annual change in FEV1 in patients with chronic obstructive pulmonary disease within the ECLIPSE study

BACKGROUND:
Change in forced expiratory volume in one second (FEV1) is important for defining severity of chronic obstructive pulmonary disease (COPD). Serological neoepitope markers of collagen turnover may predict rate of change in FEV1.

METHODS:
One thousand COPD subjects from the observatio…

Extracellular Matrix Research
1. Dec 2017

Objective Cognitive Impairment and Progression to Dementia in Women: The Prospective Epidemiological Risk Factor Study.

BACKGROUND:
Identification of subjects with a progressive disease phenotype is an urgent need in the pharmaceutical industry where most of the recent clinical trials in Alzheimer's disease have failed.

OBJECTIVES:
The objective of this study was to identify subgroups of individuals with objecti…

Hepatic System, Extracellular Matrix Research
6. Nov 2017

Inducible knockdown of procollagen I protects mice from liver fibrosis and leads to dysregulated matrix genes and attenuated inflammation

Organ fibrosis is characterized by a chronic wound-healing response, with excess deposition of extracellular matrix components. Here, collagen type I represents the most abundant scar component and a primary target for antifibrotic therapies. Liver fibrosis can progress to cirrhosis and primary live…

Gastrointestinal, Hepatitis B/C, Hepatic System
25. Oct 2017

PRO-C3: a new and more precise collagen marker for liver fibrosis in patients with chronic hepatitis C

OBJECTIVE:
Detecting significant fibrosis and cirrhosis remains important in treatment and follow-up of patients with chronic hepatitis C Infection (CHC). The aim of this study was to assess the ability of PRO-C3 to identify significant fibrosis (Ishak score ≥3) and cirrhosis (Ishak score ≥5) both …

Rheumatology, Rheumatoid Arthritis
23. Oct 2017

Blockade of GM-CSF pathway induced sustained suppression of myeloid and T cell activities in rheumatoid arthritis

OBJECTIVES:
Targeting the granulocyte-macrophage colony-stimulating factor (GM-CSF) pathway holds great potential in the treatment of inflammatory diseases. Mavrilimumab, a human monoclonal GM-CSF receptor-α antibody, has demonstrated clinical efficacy in RA. Our current study aimed to elucidate me…

Rheumatology, Osteoarthritis
16. Oct 2017

Development and use of biochemical markers in osteoarthritis: current update

PURPOSE OF REVIEW:
There is an increasing demand for noninvasive and descriptive biochemical markers (biomarkers) in osteoarthritis; for enabling early drug development (including translational research), evaluating clinical trial at an early stage and for subtyping. Purpose of the review is to rev…

Rheumatology, Osteoarthritis
14. Oct 2017

Biochemical marker discovery, testing and evaluation for facilitating OA drug discovery and development

Osteoarthritis (OA) is the most common form of joint disease. This presents the OA research community and pharmaceutical companies developing disease-modifying OA drugs (DMOADs) with great opportunities. The different OA subtypes complicate the traditional approaches for developing new treatments. I…

Gastrointestinal, Extracellular Matrix Research, Inflammatory Bowel Disease
13. Oct 2017

Ulcerative colitis, Crohn's disease, and irritable bowel syndrome have different profiles of extracellular matrix turnover, which also reflects disease activity in Crohn's disease

BACKGROUND:
Increased protease activity is a key pathological feature of inflammatory bowel disease (IBD). However, the differences in extracellular matrix remodelling (ECM) in Crohn's disease (CD) and ulcerative colitis (UC) are not well described. An increased understanding of the inflammatory pr…

Oncology, Extracellular Matrix Research
11. Oct 2017

Quantification of altered tissue turnover in a liquid biopsy: a proposed precision medicine tool to assess chronic inflammation and desmoplasia associated with a pro-cancerous niche and response to immuno-therapeutic anti-tumor modalities

Immuno-therapy has begun to revolutionize cancer treatment. However, despite the significant progress achieved in regard to the duration of clinical benefits, a substantial number of patients do not respond to these therapies. To improve the outcome of patients receiving immuno-therapy, there is a n…

Rheumatology, Osteoarthritis
28. Sep 2017

Safety, Tolerability, and Pharmacodynamics of an Anti-Interleukin-1 α/β Dual Variable Domain Immunoglobulin in Patients With Osteoarthritis of the Knee: A Randomized Phase 1 Study

OBJECTIVE:
To investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of ABT-981, a human dual variable domain immunoglobulin simultaneously targeting interleukin (IL)-1α and IL-1β, in patients with knee osteoarthritis (OA).

METHOD:
This was a randomized, double-blind, plac…

Rheumatology, Osteoarthritis
16. Sep 2017

Biomarkers for equine joint injury and osteoarthritis

We report the results of a symposium aimed at identifying validated biomarkers that can be used to complement clinical observations for diagnosis and prognosis of joint injury leading to equine osteoarthritis (OA). Biomarkers might also predict pre-fracture change that could lead to catastrophic bon…

Rheumatology, Osteoarthritis, Obesity
9. Sep 2017

A machine learning approach for the identification of new biomarkers for knee osteoarthritis development in overweight and obese women

OBJECTIVE:
Knee osteoarthritis (OA) is among the higher contributors to global disability. Despite its high prevalence, currently, there is no cure for this disease. Furthermore, the available diagnostic approaches have large precision errors and low sensitivity. Therefore, there is a need for new …

Cardiovascular System, Central Nervous System
5. Sep 2017

The Gly16 Allele of the G16R Single Nucleotide Polymorphism in the β2 -Adrenergic Receptor Gene Augments the Glycemic Response to Adrenaline in Humans

Cerebral non-oxidative carbohydrate consumption may be driven by a β2-adrenergic mechanism. This study tested whether the 46G A (G16R) single nucleotide polymorphism of the β2-adrenergic receptor gene (ADRB2) influences the metabolic and cerebrovascular responses to administration of adrenaline. Fo…

Rheumatology, Extracellular Matrix Research
30. Aug 2017

Changes of patient-reported outcomes and protein fingerprint biomarkers after exercise therapy for axial spondyloarthritis

The objective of this study was to investigate the patient-reported outcomes (PROs) and matrix metalloproteinase (MMP) derived extracellular matrix (ECM) biomarkers in non-radiographic (nr)-axial spondyloarthritis (axSpA) and radiographic (r)-axSpA after exercise intervention. Forty-six axSpA patien…

Hematology, Hemophilia
29. Aug 2017

Increased basement membrane turnover and strongly attenuated interstitial matrix turnover is a key pathological feature of haemophilia

Altered extracellular matrix (ECM) turnover is a central pathological feature of many diseases. The ECM is a meshwork of molecules that provides structural support to cells throughout the body. It consists mainly of two membranes: the interstitial matrix, which is present between parenchymal cells i…

Rheumatology, Rheumatoid Arthritis
28. Aug 2017

Suppression of active, but not total MMP-3, is associated with treatment response in a phase III clinical study of rheumatoid arthritis

OBJECTIVE:
Biologics for rheumatoid arthritis (RA) patients with moderate to severe disease may preserve joint function. Matrix metalloproteinase 3 (MMP-3), a key tissue degrading protease, is highly elevated in RA. MMP-3, which measures the total pool of circulating MMP-3 species (cMMP3), is a com…

Rheumatology, Osteoarthritis
18. Aug 2017

Sprifermin (rhFGF18) enables proliferation of chondrocytes producing a hyaline cartilage matrix

OBJECTIVE:
Fibroblast growth factor (FGF) 18 has been shown to increase cartilage volume when injected intra-articularly in animal models of osteoarthritis (OA) and in patients with knee OA (during clinical development of the recombinant human FGF18, sprifermin). However, the exact nature of this e…

Extracellular Matrix Research, Peripheral Vascular Disease
12. Aug 2017

Non-invasive evaluation of extracellular matrix remodeling in peripheral artery disease

AIM:
Peripheral artery disease (PAD) is a common manifestation of systemic atherosclerosis affecting peripheral arteries. The underlying pathology of PAD are disorganized extracellular matrix (ECM), caused by inflammation and oxidation. Previous studies have demonstrated an important structure dis…

Oncology, Lung
9. Aug 2017

Cathepsin-S degraded decorin are elevated in fibrotic lung disorders - development and biological validation of a new serum biomarker

BACKGROUND:
Decorin is one of the most abundant proteoglycans of the extracellular matrix and is mainly secreted and deposited in the interstitial matrix by fibroblasts where it plays an important role in collagen turnover and tissue homeostasis. Degradation of decorin might disturb normal tissue h…

Cardiovascular System
6. Aug 2017

Low vs. high haemoglobin trigger for transfusion in vascular surgery: protocol for a randomised trial

BACKGROUND:
In patients with cardiovascular disease, guidelines for administration of red blood cells (RBC) are mainly based on studies outside the vascular surgical setting with the recommendation to use a haemoglobin (hb) trigger-level lower than by guidelines from The European Society for Vascul…

Obesity, Rheumatology, Osteoarthritis
27. Jul 2017

Effects of dietary weight loss with and without exercise on interstitial matrix turnover and tissue inflammation biomarkers in adults with knee osteoarthritis: the Intensive Diet and Exercise for Arthritis trial (IDEA)

OBJECTIVE:
To examine the effects of dietary weight loss, with and without exercise, on selected soluble biomarkers in overweight and obese older adults with symptomatic knee osteoarthritis (OA).

DESIGN:
Blood samples were analyzed from 429 participants in the Intensive Diet and Exercise for Ar…

Renal System, Type 2-Diabetes, Obesity
26. Jul 2017

High resolution molecular and histological analysis of renal disease progression in ZSF1 fa/faCP rats, a model of type 2 diabetic nephropathy

ZSF1 rats exhibit spontaneous nephropathy secondary to obesity, hypertension, and diabetes, and have gained interest as a model system with potentially high translational value to progressive human disease. To thoroughly characterize this model, and to better understand how closely it recapitulates …

Extracellular Matrix Research
21. Jul 2017

The good and the bad collagens of fibrosis - Their role in signaling and organ function

Usually the dense extracellular structure in fibrotic tissues is described as extracellular matrix (ECM) or simply as collagen. However, fibrosis is not just fibrosis, which is already exemplified by the variant morphological characteristics of fibrosis due to viral versus cholestatic, autoimmune or…

Bone, Osteoporosis
20. Jul 2017

Targeting NSG mice-engrafting cells with a clinically applicable lentiviral vector corrects osteoclasts in Infantile Malignant Osteopetrosis

Infantile malignant osteopetrosis (IMO) is a rare, lethal, autosomal recessive disorder characterized by nonfunctional osteoclasts. More than 50% of the patients have mutations in the TCIRG1 gene, encoding for a subunit of the osteoclast proton pump. The aim of this study was to develop a clinically…

Cardiovascular System, Type 2-Diabetes
17. Jul 2017

Is cardiovascular disease in patients with diabetes associated with serum levels of MMP-2, LOX, and the elastin degradation products ELM and ELM-2?

BACKGROUND:
Diabetes mellitus type 2 (T2DM) is a significant risk factor for the development of cardiovascular diseases (CVDs). In a previous microarray study of internal mammary arteries from patients with and without T2DM, we observed several elastin-related genes with altered mRNA-expression in …

Bone
15. Jul 2017

Preventive effects of kudzu root on bone loss and cartilage degradation in ovariectomized rat

The clinical utility of Traditional Chinese Medicine (TCM) herbs/roots extracts in osteoporosis (OP) and osteoarthritis (OA) has been described in multiple reports, but there have been few studies of TCM for preventing bone loss and cartilage degradation simultaneously. Six-month-old female Sprague-…

Oncology, Colorectal
13. May 2017

Unique insight into microenvironmental changes in colorectal cancer: Ex vivo assessment of matrix metalloprotease-mediated molecular changes in human colorectal tumor tissue and corresponding non-neoplastic adjacent tissue

Matrix metalloprotease (MMP)-mediated tissue remodeling is one of the malignant changes driving colorectal cancer. Measurement of altered MMP expression/activity is not sufficient to fully understand the effect of MMP-mediated tissue remodeling. Biomarkers are required that specifically reflect the …

Central Nervous System, Biomarker position
10. May 2017

Modifiable risk factors promoting neurodegeneration is associated with two novel brain degradation markers measured in serum

There has been limited success with blood-based biomarkers of neurodegeneration. One perceived reason is that blood has no direct contact to the brain. Recently developed blood-based biomarkers of tau-degradation have shown promise as potential tools for peripheral assessment of neurodegeneration; h…

Gastrointestinal, Inflammatory Bowel Disease
8. May 2017

Misbalance in type III collagen formation/degradation as a novel serological biomarker for penetrating (Montreal B3) Crohn's disease

BACKGROUND:
Misbalances in extracellular matrix turnover are key factors in the development of stricturing (Montreal B2) and penetrating (Montreal B3) Crohn's disease.

AIM:
To determine whether serological markers for collagen formation and degradation could serve as biomarkers for complication…

Type 2-Diabetes, Obesity, Endocrinology
24. Apr 2017

The Dual Amylin- and Calcitonin-Receptor Agonist KBP-042 Works as Adjunct to Metformin on Fasting Hyperglycemia and HbA1c in a Rat Model of Type 2 Diabetes

KBP-042 is a dual amylin and calcitonin receptor agonist that increases glucose tolerance and insulin action and reduces body weight in rat models of obesity and prediabetes. The objective of the present study was to 1) evaluate KBP-042 as a treatment of late-stage type 2 diabetes in a rat model and…

Rheumatology, Hematology, Hemophilia
24. Apr 2017

Serological biomarkers detect active joint destruction and inflammation in patients with haemophilic arthropathy

INTRODUCTION:
Progressive arthropathy caused by recurrent joint bleeds is a severe complication in haemophilia.

AIM:
We investigated whether biomarkers of cartilage and bone degradation, and inflammation were altered in haemophilia patients and whether these biomarkers could identify haemophili…

Renal System, Chronic Renal Disease
21. Apr 2017

Non-invasive quantification of collagen turnover in renal transplant recipients

Kidney allograft failure due to chronic injury/rejection remains the main cause of graft loss in renal transplant recipients (RTR). Here, we investigated whether specific biomarkers of extracellular matrix (ECM) turnover are associated with allograft function and chronic kidney disease (CKD) stage i…

Chronic Renal Disease, Renal System
12. Apr 2017

Serum endotrophin, a type VI collagen cleavage product, is associated with increased mortality in chronic kidney disease

BACKGROUND:
Patients with chronic kidney disease (CKD) are at increased risk of end-stage renal disease (ESRD) and early mortality. The underlying pathophysiological processes are not entirely understood but may include dysregulation of extracellular matrix formation with accelerated systemic and r…

Endocrinology, Type 2-Diabetes
7. Apr 2017

Metabolic Syndrome, Insulin Resistance, and Cognitive Dysfunction: Does Your Metabolic Profile Affect Your Brain?

Dementia and type 2 diabetes are both characterized by long prodromal phases, challenging the study of potential risk factors and their temporal relation. The progressive relation among metabolic syndrome, insulin resistance (IR), and dementia has recently been questioned, wherefore the aim of this …

Extracellular Matrix Research, Osteoarthritis
22. Mar 2017

Biomarker of extracellular matrix remodelling C1M and proinflammatory cytokine IL-6 are related to synovitis and pain in endstage knee osteoarthritis patients

Little is known about local and systemic biomarkers in relation to synovitis and pain in end-stage osteoarthritis (OA) patients. We investigated the associations between the novel extracellular matrix biomarker, C1M, and local and systemic interleukin 6 (IL-6) with synovitis and pain. Serum C1M, pla…

Cardiovascular System, Central Nervous System
22. Mar 2017

Muscle oxygen saturation increases during head-up tilt-induced (pre)syncope

AIM:
To evaluate whether muscle vasodilatation plays a role for hypotension developed during central hypovolaemia, muscle oxygenation (Sm O2 ) was examined during (pre)syncope induced by head-up tilt (HUT). Skin blood flow (SkBF) and oxygenation (Sskin O2 ) were determined because evaluation of Sm …

Chronic Renal Disease
20. Mar 2017

Urinary collagen degradation products as early markers of progressive renal fibrosis

BACKGROUND:
Renal fibrogenesis is associated with increased ECM remodeling and release of collagen fragments in urine in progressive renal disease. We investigated the diagnostic value of urinary collagen degradation products in a proteinuria-driven fibrosis rat model with and without anti-fibrotic…

Obesity
14. Mar 2017

Optimization of Tolerability and Efficacy of Dual Amylin and Calcitonin Receptor Agonist, KBP-089, through Dose Escalation and Combination with a GLP-1 Analogue

Amylin and GLP-1 agonism induce a well-known anorexic effect at dose initiation, which is managed by dose escalation. In this study, we investigated how to optimize tolerability, while maintaining efficacy of KBP-089. Furthermore, we tested the GLP-1 add-on potential of KBP-089 in HFD rats. KBP-089 …

Lung
7. Mar 2017

Nidogen-1 Degraded by Cathepsin S can be Quantified in Serum and is Associated with Non-Small Cell Lung Cancer

Loss of basement membrane (BM) integrity is typically associated with cancer. Nidogen-1 is an essential component of the BM. Nidogen-1 is a substrate for cathepsin-S (CatS) which is released into the tumor microenvironment. Measuring nidogen-1 degraded by CatS may therefore have biomarker potential …

Type 2-Diabetes
6. Mar 2017

Weight change and risk of hyperglycaemia in elderly women

BACKGROUND:
Hyperglycaemia increases the risk of type 2 diabetes, heart disease and stroke, and is influenced by weight. However, the impact of preceding weight change on blood glycemia levels in late-life is less well understood.

AIM:
We studied the interplay between weight change and risk of …

Osteoarthritis, Rheumatology, Extracellular Matrix Research
20. Feb 2017

Chondrocyte secretome: a source of novel insights and exploratory biomarkers of osteoarthritis

The extracellular matrix (ECM) of articular cartilage is comprised of complex networks of proteins and glycoproteins, all of which are expressed by its resident cell, the chondrocyte. Cartilage is a unique tissue given its complexity and ability to resist repeated load and deformation. The mechanism…

Rheumatoid Arthritis, Rheumatology, Extracellular Matrix Research
17. Feb 2017

The minor collagens in articular cartilage

Articular cartilage is a connective tissue consisting of a specialized extracellular matrix (ECM) that dominates the bulk of its wet and dry weight. Type II collagen and aggrecan are the main ECM proteins in cartilage. However, little attention has been paid to less abundant molecular components, es…

Extracellular Matrix Research, Biomarker position, Oncology
11. Feb 2017

Excessive matrix metalloprotease-mediated degradation of interstitial tissue (type I collagen) independently predicts short-term survival in an observational study of postmenopausal women diagnosed with cancer

Extensive tissue remodeling mediated by matrix metalloproteases (MMPs) is an important part of cancer. The aim of this study was to investigate whether serum biomarkers reflecting MMP-mediated degradation of type I collagen (C1M), type IV collagen (C4M) and citrullinated vimentin (VICM) were predict…

Osteoporosis
3. Feb 2017

Forced expression of human M-CSF in CD34+ cells promotes monocyte differentiation in vitro and in vivo but blunts osteoclastogenesis in vitro

OBJECTIVES:
Here, we tested the hypothesis that human M-CSF (hM-CSF) overexpressed in cord blood (CB) CD34+ cells would induce differentiation and survival of monocytes and osteoclasts in vitro and in vivo.

METHODS:
Human M-CSF was overexpressed in cord blood CD34+ cells using a lentiviral vect…

Type 2-Diabetes
21. Jan 2017

A novel Dual Amylin and Calcitonin Receptor Agonist (DACRA), KBP-089, induces weight loss through a reduction in fat, but not lean mass, while improving food preference

BACKGROUND AND PURPOSE:
Obesity and associated co-morbidities, such as type 2 diabetes and non-alcoholic fatty liver disease, are major health challenges. Hence, there is an important need to develop weight loss therapies with the ability to reduce the co-morbidities.

EXPERIMENTAL APPROACH:
The…

Osteoarthritis
20. Jan 2017

Identification of serological biomarker profiles associated with total joint replacement in osteoarthritis patients

OBJECTIVE:
Establish a biomarker panel associated with all-cause total joint replacement (TJR) through identification of patients with osteoarthritis (OA) who do or do not progress to TJR and investigate effects of nonsteroidal anti-inflammatory drugs (NSAIDs).

DESIGN:
Serum samples from patien…

Extracellular Matrix Research
19. Jan 2017

Biomarkers of extracellular matrix turnover are associated with emphysema and eosinophilic-bronchitis in COPD

BACKGROUND:
Chronic obstructive pulmonary disease (COPD) is characterized by airflow obstruction and loss of lung tissue mainly consisting of extracellular matrix (ECM). Three of the main ECM components are type I collagen, the main constituent in the interstitial matrix, type VI collagen, and elas…

Rheumatology, Osteoarthritis
16. Jan 2017

Osteoarthritis Year in Review 2016: biomarkers (biochemical markers)

PURPOSE:
The aim of this "Year in Review" article is to summarize and discuss the implications of biochemical marker related articles published between the Osteoarthritis Research Society International (OARSI) 2015 Congress in Seattle and the OARSI 2016 Congress in Amsterdam.

METHODS:
The PubMe…

Chronic Obstructive Pulmonary Disease
11. Jan 2017

Development of a Novel Enzyme-Linked Immunosorbent Assay Targeting a Neo-Epitope Generated by Cathepsin-Mediated Turnover of Type III Collagen and Its Application in Chronic Obstructive Pulmonary Disease

A high level of extracellular matrix (ECM) turnover characterizes several lung diseases with fibrotic features. Type III collagen is one of the most abundant collagens in lung parenchyma, and cathepsins play a role in lung pathology, being responsible for tissue remodeling. In this study, we explore…

Rheumatology
5. Jan 2017

Type I and III collagen turnover is increased in axial spondyloarthritis and psoriatic arthritis. Associations with disease activity and diagnostic capacity

OBJECTIVES:
To investigate the turnover of type I and III collagen by neo-epitope markers in patients with axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA).

METHODS:
Patients with PsA (n=101) or axSpA (n=110) and healthy subjects (n=120) were included. Demographic and clinical data…