OBJECTIVETo examine serum tissue inhibitors of metalloproteinases (TIMP) -1 and -2 levels in children with nonalcoholic fatty liver disease and to investigate possible roles of the two markers.

METHODSOne hundred and five obese children were classified into 4 groups: simple obesity (n=44), simple nonalcoholic fatty liver (SNAFL, n=25), and nonalcoholic steatohepatitis (NASH, n=36). Serum TIMP-1 and -2 levels were measured using ELISA. Serum ALT and gamma-GT levels were measured with totally automatic enzymatic method.

RESULTSSerum levels of TIMP-1 and gamma-GT increased with the disease development from simple obesity to SNAFL and NASH (P<0.05). Both serum TIMP-1 and -2 levels were positively correlated with gamma-GT levels (r=0.534, P<0.01; r=0.351, P<0.05, respectively). Ninety-seven percent of children in the NASH group had serum TIMP-1 levels over 2 standard deviations of healthy controls (83.35 microg/ L) compared with 76% in the SNAFL group (P<0.05). There were no significant differences in the case proportion with TIMP-2 levels over 2 standard deviations of healthy controls between the NASH and the SNAFL groups.

CONCLUSIONSBoth TIMP-1 and -2 may reflect the state of liver fibrosis in children with nonalcoholic fatty liver disease, and serum TIMP-1 appears to be more reliable.

Adolescent ; Alanine Transaminase ; blood ; Child ; Enzyme-Linked Immunosorbent Assay ; Fatty Liver ; blood ; Female ; Humans ; Male ; Tissue Inhibitor of Metalloproteinase-1 ; blood ; Tissue Inhibitor of Metalloproteinase-2 ; blood ; gamma-Glutamyltransferase ; blood

Female ; Glioma ; blood ; diagnosis ; Humans ; Male ; Tissue Inhibitor of Metalloproteinase-1 ; blood

BACKGROUNDThe relationship between the presence of metalloproteinases and thyroid cancer remains unknown, and many controversies still exist in this field. The objective of this study was to investigate the correlations between papillary thyroid cancer and peripheral blood levels of matrix metalloproteinase-2, matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1, and tissue inhibitor of metalloproteinase-2.

METHODSThe correlations were studied by detecting the levels of matrix metalloproteinase-2, matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1, and tissue inhibitor of metalloproteinase-2 by enzyme-linked immunosorbant assay and reverse-transcription polymerase chain reaction in the peripheral blood of 30 patients with papillary thyroid carcinoma, 27 patients with benign thyroid disease, and 25 healthy volunteers.

RESULTSThe levels of matrix metalloproteinase-2, matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1, and tissue inhibitor of metalloproteinase-2 in the peripheral blood of patients with papillary thyroid carcinoma were significantly higher than those in the peripheral blood of patients with benign thyroid disease and healthy volunteers (P < 0.05). However, there were no significant differences between patients with benign thyroid disease and healthy volunteers (P > 0.05). The accuracy of detection by both enzyme-linked immunosorbant assay and reverse-transcription polymerase chain reaction in the papillary thyroid cancer group was 83.33%.

CONCLUSIONSThe levels of matrix metalloproteinase-2, matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1, and tissue inhibitor of metalloproteinase-2 in the peripheral blood are helpful in identifying thyroid carcinoma and aid in preoperative assessment.

Adult ; Aged ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Male ; Matrix Metalloproteinase 2 ; blood ; Matrix Metalloproteinase 9 ; blood ; Middle Aged ; Reverse Transcriptase Polymerase Chain Reaction ; Thyroid Neoplasms ; blood ; pathology ; Tissue Inhibitor of Metalloproteinase-1 ; blood ; Tissue Inhibitor of Metalloproteinase-2 ; blood

INTRODUCTIONGestational hypertension (GH) is a common disorder during pregnancy that can progress to preeclampsia and cause various subsequent fatal complications. A cluster of enzymes, called matrix metalloproteinases (MMPs), and its specific inhibitors, tissue inhibitors of metalloproteinases (TIMPs), have been reported to be involved in the pathophysiology of GH. The purpose of this study was to examine circulating levels of MMP-9, TIMP-1 and TIMP-2 in pregnant women who had GH and those who were normotensive.

METHODSIn a case-control study, the total levels of MMP-9, TIMP-1 and TIMP-2 in the sera of 108 pregnant patients were evaluated using enzyme-linked immunosorbent assays. 54 patients with GH (test group) and 64 normotensive pregnant women (control group) were included in the study.

RESULTSWhile MMP-9 levels showed a high level of expression in the GH group (p = 0.085), TIMP-1 and TIMP-2 levels showed low levels of expression for the same. Weak positive correlations were found on correlation analysis between maternal age and TIMP-1 in the GH group (r = 0.278, p < 0.05), and between gestational age and TIMP-2 in the control group (r = 0.318, p < 0.05).

CONCLUSIONOur findings suggest that MMP-9 may be involved in the pathophysiology of GH. It may be of value to further evaluate MMP-9 as a potential biomarker for predicting preeclampsia in pregnant women.

Adolescent ; Adult ; Biomarkers ; blood ; Case-Control Studies ; Enzyme-Linked Immunosorbent Assay ; Female ; Gestational Age ; Humans ; Hypertension, Pregnancy-Induced ; blood ; diagnosis ; Matrix Metalloproteinase 9 ; blood ; Pregnancy ; Tissue Inhibitor of Metalloproteinase-1 ; blood ; Tissue Inhibitor of Metalloproteinase-2 ; blood ; Young Adult

No abstract available.
Angina, Unstable/*enzymology/*immunology ; Female ; Humans ; Inflammation Mediators/*blood ; Interleukins/*blood ; Male ; Matrix Metalloproteinase 9/*blood ; Myocardial Infarction/*enzymology/*immunology ; Tissue Inhibitor of Metalloproteinase-1/*blood

BACKGROUNDThere is no validated blood biomarker available for glioma management. Invasive growth is the key feature of glioma. We assessed the clinical usefulness of plasma tissue inhibitor of metalloproteinase 1 (TIMP-1), which has less molecular weight than metalloproteinases, as a potential blood biomarker for glioma.

METHODSA total of 285 patients and 59 normal subjects were studied. Plasma concentration of TIMP-1 was measured with enzyme-linked immunosorbent assay. Plasma TIMP-1 was compared between normal and glioma patients, between patients with different pathological grades, and between patients with different prognoses. Longitudinal changes in plasma TIMP-1 during treatment were also evaluated. Plasma matrix metalloproteinase (MMP)-9 level was also assayed and its clinical usefulness was compared with that of TIMP-1.

RESULTSPlasma TIMP-1 and MMP-9 were both increased in glioma patients compared with normal controls (TIMP-1: P < 0.001; MMP-9: P = 0.007). Plasma TIMP-1 increases with increased tumor grade. In Grade IV gliomas, plasma TIMP-1 significantly increased after "successful removal" of the tumor (paired samples t-test, before operation vs. during chemotherapy without recurrence, t = -2.131, P = 0.038), but did not change significantly at the time of tumor recurrence (during chemotherapy without recurrence vs. after tumor recurrence, t = -0.652, P = 0.632). High plasma TIMP-1 level correlated with better survival in Grade IV glioma patients (hazard ratio: 0.550, 95% CI: 0.101-1.000, P = 0.036). In Grade IV gliomas, patients with higher plasma TIMP-1 had significantly longer survival time than those with lower plasma TIMP-1 level (25.23 vs. 18.95 months, log-rank P = 0.045). Plasma MMP-9 did not show significant association with either the pathological grade or the prognosis of glioma patients.

CONCLUSIONSPlasma TIMP-1 is associated with the diagnosis and prognosis of glioma patients. It appears to have better usefulness for guiding clinical decision making than plasma MMP-9. Further studies in an expanded patient population are needed to better define its clinical usefulness.

Adult ; Biomarkers, Tumor ; Case-Control Studies ; Female ; Glioma ; blood ; diagnosis ; Humans ; Male ; Middle Aged ; Tissue Inhibitor of Metalloproteinase-1 ; blood

OBJECTIVETo observe the effects of Shuxuening Injection (SI) on the levels of serum matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase (TIMP-1) in acute exacerbated chronic obstructive pulmonary disease (COPD) patients.

METHODSSeventy-nine patients with acute exacerbated COPD were randomly assigned to the treatment group (39 cases) and the control group (40 cases). Routine therapies for COPD were given to patients in the control group, while 15 mL SI was given to those in the treatment group by intravenous dripping, twice daily for total 14 days. The forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) were detected by Spirometer. The FEV1/FVC (%) and the FEV1% were calculated. The levels of serum MMP-9 and TIMP-1 were detected using ELISA before and after treatment, and compared with 20 healthy subjects as the control.

RESULTSThe FEV1, FVC, FEV1/FVC (%), and FEV1% were significantly improved after treatment in the treatment group when compared with before treatment and with the control group (P < 0.05, P < 0.01). When compared with before treatment and with the control group, the levels of serum MMP-9, TIMP-1, and the ratio of MMP-9/TIMP-1 decreased more significantly in the treatment group after treatment (P < 0.01). Correlation analyses showed that obvious negative correlation existed between the levels of serum MMP-9 and TIMP-1 and FEV1/FVC (%) (r = -0.677, -0.629, P < 0.01). Obvious negative correlation existed between the levels of serum MMP-9 and TIMP-1 and FEV1% (r = -0.562, -0.661, P < 0.01). Furthermore, obvious negative correlation also existed between the ratio of MMP-9/ TIMP-1 and FEV1%, as well as FEV1/FVC (%) (r = -0.732, -0.891, P < 0.01).

CONCLUSIONSSI could improve the pulmonary ventilation function of acute exacerbated COPD patients. One of its mechanisms might be correlated with lowering the serum levels of MMP-9 and TIMP-1, and correcting the imbalance of MMP-9/TIMP-1.

Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Female ; Humans ; Male ; Matrix Metalloproteinase 9 ; blood ; Middle Aged ; Phytotherapy ; Pulmonary Disease, Chronic Obstructive ; blood ; drug therapy ; Tissue Inhibitor of Metalloproteinase-1 ; blood

Actins ; biosynthesis ; genetics ; Adult ; Aged ; Female ; Hepatitis B, Chronic ; complications ; Humans ; Liver Cirrhosis ; blood ; enzymology ; virology ; Male ; Matrix Metalloproteinase 1 ; biosynthesis ; genetics ; Middle Aged ; Plasminogen Activator Inhibitor 1 ; blood ; Tissue Inhibitor of Metalloproteinase-1 ; biosynthesis ; genetics ; Urokinase-Type Plasminogen Activator ; blood

OBJECTIVETo investigate the relationship of serum metalloproteinase with the severity of liver fibrosis and inflammation.

METHODSA total of 88 patients with HBV-related liver fibrosis and early cirrhosis were enrolled from six hospitals. Serum fibrosis markers including hyaluronic acid (HA), IV collagen (IV-C), aminoterminal propeptide of type III procollagen (PIIIP), laminin (LN), matrix metalloproteinases (MMP) 1, 2, 9 and tissue inhibitors of metalloproteinase (TIMP) 1, 2 levels were determined. Liver biopsies were assessed according to a modified Scheuer and Chevallier's scoring system.

RESULTSSerum TIMP1 (r=0.540) and MMP2 (r=0.314) were correlated positively with the degree of hepatic fibrosis, whereas serum MMP1 (r=-0.495) was correlated negatively. By receiver operating curve analysis (ROC), the sensitivity to distinguish the fibrosis stage 2 from stage 1 was 90.5% and the specificity was 52.0% if the cut-off value of MMP1 was 13.96 ng/ml, and the sensitivity was 91.6% and the specificity was 64.0% if the cut-off value of TIMP1 was 76.84 ng/ml. The sensitivity to distinguish cirrhosis (stage 4) from fibrosis (stage 3) was 70.7% and specificity was 80.9% if the cut-off value of MMP1 was 6.86 ng/ml, and the sensitivity was 60.5% and the specificity was 92.3% if the cut-off value of TIMP1 was 210.04 ng/ml.

CONCLUSIONSerum TIMP1, MMP1, MMP2 levels and TIMP1/MMP1 ratio could be used as serum fibrosis markers.

Adult ; Biomarkers ; blood ; Female ; Hepatitis B, Chronic ; blood ; complications ; Humans ; Liver Cirrhosis ; blood ; virology ; Male ; Matrix Metalloproteinase 1 ; blood ; Matrix Metalloproteinase 2 ; blood ; Middle Aged ; Tissue Inhibitor of Metalloproteinase-1 ; blood

Objective: To investigate the changes of heparin-binding protein (HBP) in severe burn patients during shock stage and its effects on human umbilical vein endothelial cells (HUVECs) and neutrophils in vitro. Methods: Prospective observational and experimental research methods were used. Twenty severe burn patients who met the inclusion criteria and were admitted to the Department of Burns and Plastic Surgery of Affiliated Suzhou Hospital of Nanjing Medical University from August to November 2020 were included in severe burn group (12 males and 8 females, aged 44.5 (31.0, 58.0) years). During the same period, 20 healthy volunteers with normal physical examination results in the unit's Physical Examination Center were recruited into healthy control group (13 males and 7 females, aged 39.5 (26.0, 53.0) years). Enzyme-linked immunosorbent assay (ELISA) method was used to detect the protein expression levels of HBP and tissue inhibitor of metalloproteinase 1 (TIMP-1) in plasma of patients within 48 hours after injury in severe burn group and in plasma of volunteers in healthy control group. The correlation between protein expression of HBP and that of TIMP-1 in the plasma in the two groups was analyzed by Pearson correlation analysis. The fourth passage of HUVECs in logarithmic growth phase were used for the experiment. The HUVECs were divided into normal control group with routine culture (the same treatment below) and recombinant HBP (rHBP)-treated 12 h group, rHBP-treated 24 h group, and rHBP-treated 48 h group with corresponding treatment according to the random number table (the same grouping method below), and the mRNA expression of TIMP-1 in cells was detected by real-time fluorescence quantitative reverse transcription polymerase chain reaction. The HUVECs were divided into normal control group and rHBP-treated 48 h group with corresponding treatment, and the protein expression of TIMP-1 in the cells was detected by Western blotting. The HUVECs were divided into normal control group, rHBP alone group, aprotinin alone group, and rHBP+aprotinin group treated with the corresponding reagents (with the final molarity of rHBP being 200 nmol/L and the final concentration of aprotinin being 20 μg/mL, respectively), cultured for 48 h, and ELISA was used to detect the protein expression of TIMP-1 in the culture supernatant of cells. The neutrophils were isolated from the peripheral venous blood of the aforementioned 10 healthy volunteers by immunomagnetic bead sorting, and the cells were divided into normal control group, recombinant TIMP-1 (rTIMP-1) alone group, phorbol acetate (PMA) alone group, and rTIMP-1+PMA group treated with corresponding reagents (with the final concentration of rTIMP-1 being 500 ng/mL and the final molarity of PMA being 10 nmol/L, respectively). After being cultured for 1 h, the expression of CD63 protein in cells was detected by immunofluorescence method, the positive expression rate of CD63 protein in cells was detected by flow cytometry, and the protein expression levels of HBP and myeloperoxidase (MPO) in the culture supernatant of cells were detected by ELISA. The normal control group underwent the above-mentioned related tests at appropriate time points. The number of samples was 3 in each group of cell experiment. Data were statistically analyzed with chi-square test, Mann-Whitney U test, Kruskal-Wallis H test, and Tamhane's T2 test. Results: The protein expression levels of HBP and TIMP-1 in the plasma of patients in severe burn group were 404.9 (283.1, 653.2) and 262.1 (240.6, 317.4) ng/mL, respectively, which were both significantly higher than 61.6 (45.0, 68.9) and 81.0 (66.3, 90.0) ng/mL of volunteers in healthy control group (with Z values of -5.41 and -5.21, respectively, P<0.01). The correlation between the protein expression of HBP and that of TIMP-1 in the plasma of volunteers in healthy control group was not strong (P>0.05). The protein expression of HBP was significantly positively correlated with that of TIMP-1 in the plasma of patients in severe burn group (r=0.64, P<0.01). Compared with that in normal control group, the mRNA expression of TIMP-1 in HUVECs was significantly increased in rHBP-treated 12 h group, rHBP-treated 24 h group, and rHBP-treated 48 h group (with t values of -3.58, -2.25, and -1.26, respectively, P<0.05). Western blotting detection showed that compared with that in normal control group, the protein expression of TIMP-1 in HUVECs in rHBP-treated 48 h group was significantly enhanced. After 48 h of culture, compared with that in normal control group, the protein expression level of TIMP-1 in the culture supernatant of HUVECs in rHBP alone group was significantly increased (t=9.43, P<0.05), while the protein expression level of TIMP-1 in the culture supernatant of HUVECs didn't change significantly in aprotinin alone group or rHBP+aprotinin group (P>0.05); compared with that in rHBP alone group, the protein expression level of TIMP-1 in the culture supernatant of HUVECs in rHBP+aprotinin group was significantly decreased (t=4.76, P<0.01). After 1 h of culture, the trend of CD63 protein expression in neutrophils detected by immunofluorescence method and that by flow cytometry were consistent in each group. After 1 h of culture, compared with that in normal control group, the positive expression rate of CD63 protein in the neutrophils and the protein expression levels of HBP and MPO in the culture supernatant of cells in rTIMP-1 alone group all had no significant changes (P>0.05), while the positive expression rate of CD63 protein in the neutrophils and the protein expression levels of HBP and MPO in the culture supernatant of cells were all significantly increased in PMA alone group and rTIMP-1+PMA group (with t values of 2.41, 3.82, 5.73, 1.05, 4.16, and 1.08, respectively, P<0.05 or P<0.01); compared with that in PMA alone group, the positive expression rate of CD63 protein in the neutrophils and the protein expression levels of HBP and MPO in the culture supernatant of cells in rTIMP-1+PMA group were all significantly decreased (with t values of 5.26, 2.83, and 1.26, respectively, P<0.05 or P<0.01). Conclusions: The expression level of HBP in the plasma of severe burn patients is increased during shock stage. HBP can induce HUVECs to secrete TIMP-1 in vitro, and TIMP-1 can reduce the expression of CD63 molecule in human neutrophils.
Adult ; Antimicrobial Cationic Peptides ; Blood Proteins ; Burns ; Female ; Human Umbilical Vein Endothelial Cells ; Humans ; Male ; Neutrophils ; Tissue Inhibitor of Metalloproteinase-1