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Correlation between serological biomarkers of extracellular matrix turnover and lung fibrosis and pulmonary artery hypertension in patients with systemic sclerosis.

April 1, 2020

Int J Rheum Dis

Abstract OBJECTIVE To determine the value of serological biomarkers of collagen degradation/turnover as serum markers of organ involvement in patients with systemic sclerosis (SSc). METHODS Serum samples were obtained from 79 SSc patients and 19 healthy control subjects. Types I to VI collagen turnover, excluding type II collagen, were evaluated using nine serological biomarkers. Organ […]

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Reduced O-GlcNAcylation and tubular hypoxia contribute to the antifibrotic effect of SGLT2 inhibitor dapagliflozin in the diabetic kidney.

April 1, 2020

Am J Physiol Renal Physiol

Abstract Diabetic kidney disease is a worldwide epidemic, and therapies are incomplete. Clinical data suggest that improved renal outcomes by Na-glucose cotransporter 2 inhibitor (SGLT2i) are partly beyond their antihyperglycemic effects; however, the mechanisms are still elusive. Here, we investigated the effect of the SGLT2i dapagliflozin (DAPA) in the prevention of elevated -GlcNAcylation and tubular […]

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Addition of trans fat and alcohol has divergent effects on atherogenic diet-induced liver injury in rodent models of steatohepatitis.

March 1, 2020

Am J Physiol Gastrointest Liver Physiol

Abstract 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 essential for drug discovery. We aimed to characterize several models of steatohepatitis […]

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Increased von Willebrand Factor Processing in COPD, Reflecting Lung Epithelium Damage, Is Associated with Emphysema, Exacerbations and Elevated Mortality Risk.

January 1, 2020

Int J Chron Obstruct Pulmon Dis

Abstract 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, which is crucial for regulating the primary response of wound healing, has not […]

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The CNS-specific proteoglycan, brevican, and its ADAMTS4-cleaved fragment show differential serological levels in Alzheimer’s disease, other types of dementia and non-demented controls: A cross-sectional study.

January 1, 2020

PLoS One

Abstract Evidence indicate that the brain-specific protein, brevican, is proteolytically cleaved during neurodegeneration, hence positioning fragments of brevican as potential blood biomarkers of neurodegenerative diseases, such as dementia. We aimed to develop two assays capable of detecting the brevican N-terminal (N-Brev) and the ADAMTS4-generated fragment (Brev-A), cleaved at Ser401, in serum and to perform a […]

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Collagen fragments quantified in serum as measures of desmoplasia associate with survival outcome in patients with advanced pancreatic cancer.

December 24, 2019

Sci Rep

Abstract Pancreatic ductal adenocarcinoma (PDAC) patients have poor prognosis and poor response to treatment. This is largely due to PDAC being associated with a dense and active stroma and tumor fibrosis (desmoplasia). Desmoplasia is characterized by excessive degradation and formation of the extracellular matrix (ECM) generating collagen fragments that are released into circulation. We evaluated […]

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Collagen turnover profiles in chronic kidney disease.

November 5, 2019

Sci Rep

Abstract Renal fibrosis is a hallmark of chronic kidney disease (CKD) caused by an imbalance between formation and degradation of extracellular matrix proteins. We investigated the collagen turnover profile of 81 non-dialysis CKD stage 2-5 patients by measuring peptides reflecting formation and degradation of collagen type (COL) I, III, IV, and VI. Based on the […]

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Extracellular Matrix Fragments of the Basement Membrane and the Interstitial Matrix Are Serological Markers of Intestinal Tissue Remodeling and Disease Activity in Dextran Sulfate Sodium Colitis.

November 1, 2019

Dig Dis Sci

Abstract BACKGROUND Chronic intestinal inflammation results in tissue damage partly caused by an increase in matrix metalloproteinases (MMP) activity causing degradation of extracellular matrix (ECM) proteins. We studied intestinal tissue remodeling by quantifying ECM protein fragments in serum in dextran sulfate sodium (DSS)-induced colitis, to investigate ECM protein fragments as serological biomarkers of intestinal tissue […]

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Mechanisms of vascular permeability and remodeling associated with hemarthrosis in factor VIII-deficient mice.

November 1, 2019

J Thromb Haemost

Abstract BACKGROUND Vascular remodeling associated with hemophilic arthropathy (HA) may contribute to bleed propagation, but the mechanisms remain poorly understood. OBJECTIVES To explore molecular mechanisms of HA and the effects of hemostasis correction on synovial vascular remodeling after joint injury in hypocoagulable mice. METHODS Factor VIII (FVIII)-deficient mice +/- FVIII treatment and hypocoagulable wild-type mice […]

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