98%
921
2 minutes
20
Alteration of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) expression has been studied for various cardiac diseases, including dilated cardiomyopathy (DCM), with the significance of surrogate markers of extracellular matrix (ECM) remodeling. In this study, we determined the MMP-8, MMP-9 and TIMP-2 immunoexpression in the heart of patients diagnosed with DCM in relation to a histological composite score (HCS). The study included 40 cases of heart fragments that were processed by the usual paraffin inclusion technique, followed by a semi-quantitative evaluation of histopathological parameters, which summed, allowed the establishment of a HCS. Subsequently, the cases were immunohistochemically processed for MMP-8, MMP-9 and TIMP-2, followed by the semi-quantitative evaluation of their expression intensity. MMP-8 was identified only in myocardiocytes, while MMP-9 and TIMP-2 were present in both myocardiocytes and stroma, but with different intensity. The increasing intensity of MMP-8 and TIMP-2 immunoreactions was significantly associated with low HCS. In case of MMP-9, the immunostaining intensity analysis in relation to the HCS level revealed insignificant differences, but we found an association of increased and moderate intensity with low HCS. The imbalance between TIMPs and MMPs disrupts the ECM architecture and contributes to the remodeling process in DCM, aspect that can be used in the development of new clinical therapies.
Download full-text PDF |
Source |
---|
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 PDFInt J Mol Sci
August 2025
Laboratory of Cutaneous Physiopathology and Integrated Center of Metabolomics Research, San Gallicano Dermatological Institute, IRCCS, 00144 Rome, Italy.
The Tumour Microenvironment (TME) is pivotal for melanoma progression and contributes to therapy resistance. While dermal cell involvement is well established, the role of epidermal cells remains less defined. To explore the contribution of Normal Human Keratinocytes (NHKs) to melanoma biology, we investigated the modification of gene and protein expression of NHKs exposed to melanoma-conditioned medium or maintained in a co-culture system.
View Article and Find Full Text PDFIran J Biotechnol
April 2025
Department of Nephrology, Taixing People's Hospital, Taixing, Jiangsu 225400, China.
Background: Renal fibrosis is a key pathological process in chronic kidney disease (CKD), characterized by excessive extracellular matrix (ECM) deposition and epithelial-mesenchymal transition (EMT). Current treatment strategies have limited efficacy, necessitating the exploration of novel therapeutic agents. Eicosapentaenoic acid (EPA), a bioactive marine-derived omega-3 polyunsaturated fatty acid, has shown promise in modulating fibrosis-related signaling pathways.
View Article and Find Full Text PDFCirc J
August 2025
Department of Cardiac Surgery, Nagoya University Graduate School of Medicine.
Background: The pathogenesis of aortic aneurysm (AA) is characterized by chronic inflammation of the aortic wall, the associated accumulation of macrophages, and degradation of the extracellular matrix, including elastin. Colchicine (COL) has long been known for its anti-inflammatory effects, so in this study we investigated its effects on AA.
Methods And Results: In vitro, tumor necrosis factor (TNF)-α-stimulated macrophages and vascular smooth muscle cells (VSMCs) were treated with and without COL for 24 h.
Biomed 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 PDF