Serum levels of matrix metalloproteinase 9 and 19 in the patients with pneumoconiosis / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To measure peripheral serum levels of matrix metalloproteinase 9 (MMP9) and matrix metalloproteinase 19 (MMP19) in patients with pneumoconiosis, and to investigate their feasibility as potential biomarkers for pneumoconiosis.</p><p><b>METHODS</b>Ninety-eight male patients with pneumoconiosis (49 patients in phase I, 36 patients in phase II, and 13 patients in phase III) were enrolled as subjects, which included 41 patients with silicosis and 57 patients with coal workers' pneumoconiosis. Ninety-eight healthy male physical examinees were used as controls. A fasting blood sample (3 ml) was collected from the peripheral venous blood of each patient or control, and the serum was separated from the blood sample. The expression levels of MMP9 and MMP19 in serum were measured by enzyme-linked immunosorbent assay.</p><p><b>RESULTS</b>Serum levels of MMP9 and MMP19 in patients with silicosis or coal workers' pneumoconiosis were significantly lower than those in the control group (P < 0.05). Serum levels of MMP19 in patients with silicosis were significantly higher than those in patients with coal workers' pneumoconiosis (P < 0.05). Serum levels of MMP19 in patients exposed to dust for less than 7 years were significantly higher than those in patients exposed to dust for more than 20 years (P < 0.05). There were no significant differences in serum levels of MMP9 and MMP19 between patients with different levels of pulmonary function impairment (P > 0.05). Serum expression levels of MMP9 and MMP19 were positively correlated with each other in both patients with pneumoconiosis and those in the control group (P < 0.05). The serum expression level of MMP9 was negatively correlated with the stage of pneumoconiosis (P < 0.05).</p><p><b>CONCLUSION</b>Serum MMP9 and MMP19 may be used as potential biomarkers for pneumoconiosis.</p>

Expression and significance of MMP-26, TIMP-4 and MMP-9 in diffuse large B-cell lymphoma cells / 中国实验血液学杂志

The aim of this study was to investigate the expression of matrix metalloproteinase 26 (MMP-26), tissue inhibitor of metalloproteinase-4 (TIMP-4) and matrix metalloproteinase 9 (MMP-9) in patients with diffuse large B cell lymphoma (DLBCL) and their correlations with pathogenesis and development of DLBCL. A total of 95 specimens excised from DLBCL patients were prepared. Expression of MMP-26, TIMP-4 and MMP-9 were tested by SABC immunohistochemistry method and its correlation to clinicopathology indexes were analyzed. The results showed that as compared with reactive hyperplasia of lymph nodes, the high expression of MMP-26, TIMP-4 and MMP-9 were found in different types of DLBCL. The positive expression rate of MMP-26 was related to immune typing (P < 0.05). The expression level of MMP-26 in GCB was lower than that in non-GCB, and did not relate to clinical staging, age, sex, diseased region (P > 0.05). The positive expression rate of MMP-9 was related to clinical staging, the positive expression rate of MMP-9 proteins in patient at III and IV stage was obviously higher than that in patients at I and II stage, but did not relate to immune type, age, sex and diseased region of DLBCL (P > 0.05). The expression of TIMP-4 did not relate to immune type, clinical stage, age, sex, disease region (P > 0.05). The expression of MMP-26 in pathologic tissue of DLBCL did not relate to expression of TIMP-4, but positively related to expression of MMP-9 protein (r = 0.486, P < 0.05). It is concluded that MMP-26 and MMP-9 synergically express in DLBCL. MMP-26 may be involve in pathogenesis and invasiveness of DLBCL, the expression of MMP-26 relates to subtypes of DLBCL. The MMP-26 may serve as an indicator for typing of DLBCL and contributes to predict the invasion and metastasis of DLBCL and itself may become a potential target for therapy.

Triptolide inhibits ovarian cancer cell invasion by repression of matrix metalloproteinase 7 and 19 and upregulation of E-cadherin

Triptolide, a compound extracted from the traditional Chinese medicine preparation of Tripterygium wilfordii Hook F., has been reported to have anti-inflammatory and anti-cancer activities. However, its effect on ovarian cancer invasion is unknown. We observed that MMP7 and MMP19 expression increased in ovarian cancer tissue. Triptolide treatment inhibited the migration and invasion of ovarian cancer cells SKOV3 and A2780 at the concentration of 15 nM. We also observed that triptolide suppressed MMP7 and MMP19 promoter activity in a dose-dependent manner, down-regulating the expressions of these promoters on mRNA and protein level. Moreover, triptolide enhanced E-cadherin expression in ovarian cancer cells. In vivo, triptolide inhibited tumor formation and metastasis in nude mice, and suppressed MMP7 and MMP19 expression; it also enhanced E-cadherin expression in tumor in a dose-dependent manner. Over expression of MMP7 and MMP19, or suppression of E-cadherin expression partially abolished the inhibitory effect of triptolide on invasion of ovarian cancer cells. To summarize, triptolide significantly inhibited the migration and invasion of ovarian cancer cells by suppression of MMP7 and MMP19 and up-regulation of E-cadherin expression. This study shows that triptolide is a good candidate for the treatment of ovarian cancer and reduction of metastasis.

The roles of Kupffer cells in the development and regression of liver fibrosis / 药学学报

Hepatic fibrosis results from iterative hepatic injury with sustained inflammation, formation of scar tissue, loss of tissue architecture and organ failure. There is no doubt, from both human and animal studies, that too much or too protracted inflammation in the liver leads to excess scarring. During liver injury, Kupffer cells can quickly flood the hepatic milieu with soluble mediators, including oxidants, cytokines, and proteinases, which can affect stellate cell proliferation, migration, and differentiation. On the other hand, the contribution of Kupffer cells to regression of hepatic fibrosis has been demonstrated. These findings underscore the potential importance of hepatic macrophages in regulating both stellate cell biology and extracellular material degradation during regression of hepatic fibrosis. Therefore, biological characterization of Kupffer cells, their interactions with stellate cells in the cytokine environment are essential to understand the mechanisms underlying the progressive development of excessive scarring in the liver as well as the ability of the liver for tissue repair and recovery.

Effects of intra-articular injection of p38 mitogen-activated protein kinase inhibitor on matrix metalloproteinase in articular cartilage of a rat model of osteoarthritis / 中国医学科学院学报

<p><b>OBJECTIVE</b>To observe the effect of intra-articular injection of SB203580, a selective p38 mitogen-activated protein kinase inhibitor, on the expression of matrix metalloproteinase (MMP)-3, MMP-13 in a rat model of osteoarthritis (OA) and to explore the relationship between the MMP-3/MMP-13 expressions and the severity of OA.</p><p><b>METHODS</b>Fourty SD rats underwent unilateral anterior cruciate ligament transection (ACLT) and then randomly divided into four groups, with 10 rats in each group. Group A received 0.1 ml intra-articular injection of SB203580 at a high concentration of 100 micromol/L (once a week) immediately after surgery, and group B were treated under the same condition using SB203580 with a low concentration of 10 micromol/ L Group C received 0.1 ml intra-articular normal saline, and group D were not injected as controls after ACLT. All rats were sacrificed seven weeks after the surgery. Macroscopic and immunohistochemical studies were performed on the cartilage. Protein expressions of MMP-3 and MMP-13 were determined by Western blot. RESULTS Cartilage degradation was significantly milder in group A and group B than in the control groups, as shown by morphological studies (P < 0. 05) and immunohistochemical studies (P < 0. 05). The protein expressions of MMP-3 and MMP-13 in cartilage were significantly lower in groups A and B than in groups C and D (P < 0.01).</p><p><b>CONCLUSION</b>SB203580 can inhibit the expressions of MMP-3 and MMP-13 and thus protect the cartilage.</p>

Differential expression of a homing-related molecule repertoire among umbilical cord blood, mobilized peripheral blood and bone marrow-derived hematopoietic stem/progenitor cells / 中华血液学杂志

<p><b>OBJECTIVE</b>To compare the expression profiles of a set of homing-related molecules (HRM) repertoire expressed on hematopoietic stem/progenitor cells (HS/PC) from different sources.</p><p><b>METHOD</b>The expression levels of HRM on HS/PC from umbilical cord blood (UCB), mobilized peripheral blood (mPB) and bone marrow (BM) were assessed using a highly sensitive 4-color flow cytometric analysis.</p><p><b>RESULTS</b>UCB-derived CD34(bright) cells, as well as mPB- and BM-derived CD34(bright) cells strongly expressed CD44, CD11a, CD18, CD62L, CD31 and CD49d. On the other hand, significantly lower expressions of CD49e, CD49f, CXCR-4 and CD54 on UCB-derived CD34(bright) and CD34(bright)CD38(-) cells, compared with those on mPB- and BM-derived CD34(bright) and CD34(bright)CD38(-) cells, were observed. None of UCB-, mPB- and BM-derived CD34(bright) cells expressed other chemokine receptors, including CCR-1, CCR-2, CCR-3, CCR-5, CXCR-1, CXCR-2, CXCR-3 and CXCR-5. Another striking finding was that only mPB-derived CD34(bright) cells expressed significant levels of both the matrix metalloproteinases MMP-2 \[(11.4 +/- 4.9)%\] and MMP-9 \[(27.6 +/- 7.8)%\].</p><p><b>CONCLUSION</b>HS/PC from UCB have some defects of expression of HRM repertoire, which might partly explain the cause(s) of delayed hematopoietic reconstitution after UCB transplant.</p>