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Background: Circulating levels of tissue inhibitor of metalloproteinase (TIMP)-1 and matrix metalloproteinase (MMP)-2 are investigated as parameters for the diagnosis of fibrosis in chronic liver disease. We evaluated their diagnostic potential in comparison to hepatic histology, serum hyaluronate and standard liver function tests.
Methods: Commercially available ELISA assays were used to study circulating values of TIMP-1 and MMP-2 (Bindazyme, Biotrak, Quantikine) in patients with chronic hepatitis C (CAH; n=59), hepatitis C virus-induced cirrhosis (n=19) and 30 healthy controls. Hepatic histology was evaluated using the Hepatitis-Activity-Index according to Ishak et al. [J. Hepatol., 22 (1995) 696-699], quantifying separately inflammatory activity and fibrosis.
Results: Normal ranges for TIMP-1 and MMP-2 values differed for the different assays. Nevertheless, the various assays showed similar diagnostic ability and linear correlation. MMP-2 values were similar in controls and in CAH patients with and without fibrosis, but increased significantly in cirrhosis. TIMP-1 values showed a steady increase from normal to CAH without fibrosis, hepatitis with fibrosis, and cirrhosis. The diagnostic potential of serum MMP-2 to detect fibrosis was low with a sensitivity of 7% in the two assays used and an overall diagnostic efficiency of 56% and 58%. The potential of circulating MMP-2 to detect cirrhosis was higher with sensitivities of 74% and 83% and specificities of 96% and 100%, resulting in a diagnostic efficiency of 92% in the different assays. Plasma TIMP-1 values detect fibrosis with a sensitivity of 52% and 67% and a specificity of 68% and 88% resulting in overall efficiency rates of 68% and 71%, respectively. TIMP-1 values detect cirrhosis with 100% sensitivity but only 56% and 75% specificity. The diagnostic potential of circulating TIMP-1 was similar to that of hyaluronate and better than that of enzymes or albumin values.
Conclusion: Plasma values of TIMP-1 and MMP-2 are able to detect cirrhosis with high sensitivity. TIMP-1 values also detect fibrosis with comparable efficiency. Regular determinations of both TIMP-1 and MMP-2 in CAH patients may be used as indicators of increasing fibrosis and the development of cirrhosis.
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http://dx.doi.org/10.1016/s0009-8981(01)00730-6 | DOI Listing |
Int J Biol Macromol
September 2025
Fujian Key Laboratory of Oral Diseases & Fujian Provincial Engineering Research Center of Oral Biomaterial & Stomatological Key Laboratory of Fujian College and University, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, 350000, China; Research Center of Dental Esthetics and B
This study examined the pH-dependent (3, 5, and 7) regulation of matrix metalloproteinase (MMP) activity by cathepsin K (catK) and glycosaminoglycans (GAGs) using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), fluorescence assays, and human dentin slice experiments. The direct effects of catK were evaluated in the catK-active, catK-deficient, and odanacatib (ODN)-inhibited groups, whereas indirect GAG/ tissue inhibitor of metalloproteinase (TIMP)-mediated regulation was assessed in the catK-active, ODN-inhibited, and chondroitin sulfate (CS)-treated groups through dimethylmethylene blue (DMMB) assays, in situ zymography, and immunofluorescence staining. CatK directly activated MMP-2 (62 kDa) and MMP-9 (82 kDa) at all pH values, with no activation observed in the ODN-inhibited or catK-deficient groups.
View Article and Find Full Text PDFSci Rep
September 2025
Pharmacology Department, Medical Research and Clinical Studies Institute, National Research Centre (ID: 60014618), 33 ELBohouth St. (former EL Tahrir St.), P.O. 12622, Dokki, Cairo, Egypt.
Idiopathic pulmonary fibrosis (IPF) is one of the rapidly progressing interstitial lung illnesses. Bleomycin (Bleo) is used as a chemotherapeutic agent for the treatment of lymphoma patients. The major side effects of Bleo include lung fibrosis, characterized by the accumulation of inflammatory cells.
View Article and Find Full Text PDFBiomed Pharmacother
September 2025
Cardiovascular Disease Program, Monash Biomedicine Discovery Institute and Department of Pharmacology, Monash University, Clayton, Victoria, Australia. Electronic address:
Idiopathic pulmonary fibrosis (IPF) is a fatal condition associated with excessive interstitial collagen accumulation and irreversible lung function decline, for which there is no effective cure. Hence, this study evaluated the dose-dependent anti-fibrotic effects of bone marrow mesenchymal stem cell-derived extracellular vesicles (BM-MSC-EVs) in transforming growth factor (TGF)-β1-stimulated human dermal myofibroblasts (1 ×10-1 ×10 BM-MSC-EVs) and TGF-β1-stimulated lung myofibroblasts isolated from non-IPF versus and IPF patients (1 ×10-1 ×10 BM-MSC-EVs) after 72 h in culture; and when intranasally-administered therapeutically (from days 21-28 post-injury) to bleomycin (BLM)-injured mice (2.5 ×10-2.
View Article and Find Full Text PDFPharmacol Rep
July 2025
Department of Pediatric Surgery and Urology, Medical University of Białystok, Waszyngtona 17, Białystok, 15-274, Poland.
Background: Infantile hemangiomas (IH) are the most prevalent benign vascular tumors diagnosed in the pediatric population. Propranolol, a nonselective beta-adrenergic receptor antagonist, is the first-line treatment for IH. In this study, we aimed to assess the changes in plasma levels of HIF-1α, MMP-2, MMP-9, and TIMP-1 in patients with IH before and after one month of propranolol treatment.
View Article and Find Full Text PDFInt Immunopharmacol
September 2025
Experimental Medicine Research Center, Tehran University of Medical Sciences (TUMS), Tehran, Iran; Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:
Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal lung disease characterized by excessive extracellular matrix (ECM) accumulation, fibroblast activation, and chronic inflammation. This study examined the antifibrotic effects of naltrexone (NTX), an opioid receptor antagonist, in a bleomycin (BLM)-induced pulmonary fibrosis model in Wistar rats. Daily administration of NTX significantly reduced alveolar wall thickening, collagen deposition, and histopathological injury scores.
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