Effects of Muscone on Cartilage Morphology and Matrix Metalloproteinases-3 (MMP-3h) and Matrix Metalloproteinases-9 (MMP-9) Expression in Rheumatoid Arthritis Rat Models

Aim: To discuss Muscone treatment in Rheumatoid Arthritis Rat Models and relative mechanisms. Materials and methods: Dividing 36 rats as 4 groups as Normal, Model, DMSO and Muscone groups (n = 9). Rats of Model, DMSO and Muscone groups were made Rheumatoid Arthritis model. Muscone group were treated with 2 mg/kg Muscone after modeling. HE staining and Masson staining were used to observe the morphological changes of cartilage tissue, measuring MMP-3 and MMP-9 expression by RT-PCR, Western Blotting (WB) and Immunohistochemistry (IHC). Results: Compared with Model group, the pathological changes of Muscone group was significantly improved and average optical density of collagen fibers was significantly depressed (P < 0.001, respectively) via MMP-3 and MMP-9 proteins significantly depressing (P < 0.001, respectively). Conclusion: Muscone improved Rheumatoid Arthritis by depressing MMP-3 and MMP-9 proteins in vivo study.

Landscape Analysis of Matrix Metalloproteinases Unveils Key Prognostic Markers for Patients With Breast Cancer

Breast cancer (BRCA) is the most common cancer in the world, of which incidence rate and mortality are the highest in women. Being responsible for the remodeling and degradation of extracellular matrix proteins, matrix metalloproteinases (MMPs) have been regarded as one of the most important protease family related to tumorigenesis. It has been demonstrated that MMPs play crucial roles in some tumor invasion and metastasis. However, the potential roles of MMPs in tumorigenesis and progression of BRCA and its subtype remain elusive. Herein, we conducted a systematic study on MMPs via a series of database-based retrospective analysis, including TCGA, R Studio, GEPIA, Kaplan-Meier Plotter, cBioPortal, STRING, GeneMANIA and TIMER. As a result, many MMP family members were differentially expressed in patients with BRCA, e.g., the expressions of MMP1, MMP9, MMP11 and MMP13 were up-regulated, whereas the expression levels of MMP19 and MMP28 were down-regulated. MMP9, MMP12, MMP15 and MMP27 were significantly correlated with the clinical stages of BRCA, implying their important roles in the occurrence and development of BRCA. In addition, the survival analysis indicated that different expression pattern of MMPs exhibited distinct outcomes in patient with BRCA, e.g., patients with high expression of MMP2, MMP8, MMP16, MMP17, MMP19, MMP20, MMP21, MMP24, MMP25, MMP26 and MMP27 had a prolonged survival time, while the others (MMP1, MMP7, MMP9, MMP12 and MMP15) exhibited poor prognosis. Subsequent functional and network analysis revealed MMPs were mainly correlated with parathyroid hormone synthesis and secretion pathway, collagen metabolism, and their effect on the activities of serine hydrolase, serine peptidase and aminopeptidase. Notably, our analysis showed that the expression of MMPs was significantly correlated with the infiltration of various immune cells in BRCA, including CD8+T cells, CD4+T cells, macrophages, neutrophils, B cells, and dendritic cells, suggesting the close correlations between MMPs and immune functions. In short, our study disclosed MMPs play multiple biological roles in the development of BRCA, MMP1 and MMP9 might be used as independent prognostic markers and potential therapeutic targets for diagnosis and treatment for patients with BRCA.

Features of the level of matrix metalloproteinase-2, -3, -9 and tissue inhibitors of metalloproteinases-1, -2, -3, -4 in the aqueous humor of patients with primary open-angle glaucoma

Aim. To study the content of matrix metalloproteinase (MMP)-2, -3, -9 and tissue inhibitors of metalloproteinases (TIMPs) -1, -2, -3, -4 in the aqueous humor of patients with moderate primary open-angle glaucoma (POAG).Materials and methods. The experimental group included 47 patients with verified moderate primary open-angle glaucoma. The control group consisted of 26 patients with uncomplicated cataract. The levels of MMP-2, -3, -9 were determined with Luminex Performance Human MMP Magnetic Panel 3-plex kit (R&D Systems, USA), the concentration of TIMPs-1, -2, -3, - 4 was determined with the Human TIMP Magnetic Luminex Performance Assay 4-plex kit (R&D Systems, USA). The study was carried out using flow-through field fluorometry on a Bio-Plex 200 double-beam laser analyzer (Bio-Rad, USA).Results. The study showed a statistically significant increase in the levels of matrix metalloproteinase-2 and tissue inhibitors of matrix metalloproteinases-1, -2, -3, -4 in the aqueous humor of patients with moderate POAG compared with patients with uncomplicated cataract.Conclusion. The obtained data on high concentrations and imbalance in the levels of matrix metalloproteinases and their tissue inhibitors in the aqueous humor of patients with moderate POAG confirm the role of local inflammation, as well as impairments in the structure of the extracellular matrix and its remodeling in the mechanisms of development of this pathology.