OBJECTIVE: This study aims to detect the levels of mucin (MUC)-4, metalloproteinase (MMP)-7, and MMP-8 in peri-implant crevicular fluid (PICF) and investigate whether the novel combinations of MMP-7 and MUC-4 are effective markers of peri-implant diseases, particularly when used in the PICF of healthy individuals, to provide a theoretical basis for finding a novel reference index that can aid the diagnosis, evaluation, and treatment of peri-implant diseases.
METHODS: A total of 63 subjects with 2-5 years of upper prosthesis loading were selected according to inclusion and exclusion criteria, composed of 24 controls and 39 patients with peri-implantitis (PI) group. MUC-4, MMP-7, and MMP-8 levels were detected through enzyme linked immunosorbent assay (ELISA).
RESULTS: No significant differences in age, sex, and other parameters were found between the PI and control groups. The PI group had higher MMP-7 and MMP-8 expression levels (P<0.05) but lower MUC-4 level (P<0.001). Correlation analysis showed that MMP-7 was positively correlated with pocket probing depth (PPD) (r=0.451, P<0.001); MMP-8 was positively correlated with PPD, bleeding on probing (BOP), and gingival index (GI) (r=0.619, P<0.001; r=0.478, P<0.001; r=0.332, P=0.009). MUC-4 was negatively correlated with PPD, BOP, and GI (r=-0.492, P<0.001; r=-0.321, P=0.010; r=-0.396, P=0.001). MMP-7, MMP-8, and MUC-4 had certain diagnostic efficacy for PI. MMP-8 exhibited the best diagnostic efficacy for PI. When the cutoff value of MMP-8 was >21.21, the area under the curve (AUC) was 0.868, and the sensitivity and specificity for the diagnosis of PI were 0.96 and 0.68, respectively. The diagnostic efficacy of MMP-7 and MUC-4 parallel diagnostic models was higher than that of each factor, and the diagnostic sensitivity of the model for PI was 0.96, and the specificity was 0.56.
CONCLUSIONS: Differences in MMP-7 and MUC-4 levels were found between the inflammation and control groups and may be diagnostic indicators for predicting PI; combinations of MMP-7 and MUC-4 had a good diagnostic value for inflammation.
目的: 探讨基质金属蛋白酶（MMP）-7、MMP-8和黏蛋白（MUC）-4在种植体周围龈沟液（PICF）中的水平，分析二者是否具有区分种植体周围疾病与健康个体的能力，以期为寻找辅助种植体周围疾病诊断、评估和治疗的新型参考指标提供理论基础。方法: 按照纳入和排除标准选择上部修复体负载2~5年的63位受试者，其中对照组24例，种植体周围炎（PI）组39例。收集受试者一般情况及种植体周围临床指标，X线片测量牙槽骨吸收量，酶联免疫吸附试验法（ELISA）检测PICF中的MUC-4、MMP-7、MMP-8水平。结果: PI组和对照组受试者的年龄、性别等参数信息差异无统计学意义，PI组MMP-7（P<0.05）、MMP-8（P<0.001）的表达水平均高于对照组，PI组MUC-4表达水平低于对照组（P<0.001）；相关性分析显示，MMP-7与牙周探诊深度（PPD）呈正相关（r=0.451，P<0.001）；MMP-8分别与PPD、探诊出血（BOP）、牙龈指数（GI）呈正相关（r=0.619，P<0.001； r=0.478，P<0.001； r=0.332，P=0.009）；MUC-4分别与PPD、BOP、GI呈负相关（r=-0.492，P<0.001； r=-0.321，P=0.010； r=-0.396，P=0.001）。MMP-7、MMP-8、MUC-4对PI均具有一定的诊断效能，其中MMP-8对PI的诊断效能最好，当MMP-8>21.21时，其曲线下面积为0.868，诊断PI的灵敏度为0.96、特异度为0.68；MMP-7、MUC-4并联诊断模型的诊断效能高于两种因子单独诊断，模型对PI的诊断灵敏度为0.96，特异度为0.56。结论: MMP-7、MUC-4的水平在PI组与对照组之间差异有统计学意义，可能成为预测是否罹患PI的诊断指标；联合MMP-7、MUC-4对炎症具有较好的诊断价值。.

Previous work showed that matrix metalloproteinase-7 (MMP-7) regulates colon cancer activities through an interaction with syndecan-2 (SDC-2) and SDC-2-derived peptide that disrupts this interaction and exhibits anticancer activity in colon cancer. Here, to identify potential anticancer agents, a library of 1,379 Food and Drug Administration (FDA)-approved drugs that interact with the MMP-7 prodomain were virtually screened by protein-ligand docking score analysis using the GalaxyDock3 program. Among five candidates selected based on their structures and total energy values for interacting with the MMP-7 prodomain, the known mechanistic target of rapamycin kinase (mTOR) inhibitor, everolimus, showed the highest binding affinity and the strongest ability to disrupt the interaction of the MMP-7 prodomain with the SDC-2 extracellular domain in vitro. Everolimus treatment of the HCT116 human colon cancer cell line did not affect the mRNA expression levels of MMP-7 and SDC-2 but reduced the adhesion of cells to MMP-7 prodomain-coated plates and the cell-surface localization of MMP-7. Thus, everolimus appears to inhibit the interaction between MMP-7 and SDC-2. Everolimus treatment of HCT116 cells also reduced their gelatin-degradation activity and anticancer activities, including colony formation. Interestingly, cells treated with sirolimus, another mTOR inhibitor, triggered less gelatin-degradation activity, suggesting that this inhibitory effect of everolimus was not due to inhibition of the mTOR pathway. Consistently, everolimus inhibited the colony-forming ability of mTOR-resistant HT29 cells. Together, these data suggest that, in addition to inhibiting mTOR signaling, everolimus exerts anticancer activity by interfering with the interaction of MMP-7 and SDC-2, and could be a useful therapeutic anticancer drug for colon cancer.NEW & NOTEWORTHY The utility of cancer therapeutics targeting the proteolytic activities of MMPs is limited because MMPs are widely distributed throughout the body and involved in many different aspects of cell functions. This work specifically targets the activation of MMP-7 through its interaction with syndecan-2. Notably, everolimus, a known mTOR inhibitor, blocked this interaction, demonstrating a novel role for everolimus in inhibiting mTOR signaling and impairing the interaction of MMP-7 with syndecan-2 in colon cancer.

UNASSIGNED: To explore the advantages of urinary matrix metalloproteinase-7 (MMP-7) in evaluating renal tubular injury in minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) patients compared with urinary cystatin C (CysC) and retinol-binding protein (RBP).
UNASSIGNED: Serum and urine samples were collected from 20 healthy volunteers, and 40 MCD and 20 FSGS patients. Serum and urinary MMP-7 levels were measured by enzyme-linked immunosorbent assay. Urinary total protein, CysC and RBP levels were measured by automatic specific protein analyzer and compared with urinary creatinine level for calibration. The renal tissue serial sections were stained by MMP-7 immunohistochemistry and periodic acid-Schiff.
UNASSIGNED: Under light microscopy, MMP-7 granular weak positive expression was showed sporadically in the cytoplasm of a few renal tubular epithelial cells without obvious morphological changes in MCD patients, and MMP-7-positive expression was observed in the cytoplasm of some renal tubular epithelial cells in FSGS patients. There was no significant difference in serum MMP-7 level among the three groups. Compared with the control group, the urinary MMP-7 level in MCD patients was higher, but urinary CysC and RBP levels were not increased significantly. Compared with the control group and MCD patients, urinary MMP-7, CysC and RBP levels in FSGS patients were upregulated significantly.
UNASSIGNED: Urinary MMP-7 could not only evaluate the mild renal tubular epithelial cells injury in MCD patients with massive proteinuria, but also evaluate the continuous renal tubular epithelial cells injury in FSGS patients.

OBJECTIVE: Serum matrix metalloproteinase-7 (MMP-7) levels can precisely differentiate biliary atresia (BA) from non-BA cholestasis. However, serum MMP-7 levels of some BA patients were within normal range or slightly elevated. This study aimed to investigate the clinical characteristics and prognosis of biliary atresia with low serum MMP-7 levels.
METHODS: This is a retrospective cohort study. Cases of BA from July 2020 to December 2022 were consecutively enrolled. They were divided into low-MMP-7 group (MMP-7 ≤ 25 ng/ml) and high-MMP-7 group (MMP-7 > 25 ng/ml) according to serum MMP-7 levels preoperatively. The perioperative clinical characteristics, the 3-month and 6-month jaundice clearance rate post-Kasai procedure, and the native liver survival were compared between the two groups.
RESULTS: A total of 329 cases were included in this study, 40 of which were divided into the low-MMP-7 group. Preoperative GGT and direct bilirubin levels in the low-MMP-7 group were significantly lower than those in the high-MMP-7 group (258.6 U/L, interquartile range [IQR]: 160.4411.6 vs. 406.8 IU/L, IQR: 215,655.0, P = 0.0076; 103.8 μmol/L, IQR: 79.0,121.4 vs. 115.3 μmol/L, IQR: 94,138.8, P = 0.0071), while the gender, the day at surgery and preoperative ALT, AST, TBA, total bilirubin levels showed no significant differences (P > 0.05). The 3-month and 6-month jaundice clearance rate post-Kasai procedure in the low-MMP-7 group were lower than those in the high-MMP-7 group (29.73% vs. 53.09%, P = 0.049; 32.14% vs. 54.73%, P = 0.023). The 1-year native liver survival rate was 29.63% for the low-MMP-7 group and 53.02% for the high-MMP-7 group (P = 0.022).
CONCLUSIONS: Preoperative clinical characteristics were similar between low-MMP-7 group and high-MMP-7 group, while patients with low serum MMP-7 levels showed worse prognosis, indicating that this might be listed as a new clinical subtype of BA which could contribute to designing new treatment strategies for BA in the future.
METHODS: Cohort Study.
METHODS: Level II.

OBJECTIVE: The liver is a common site of cancer metastasis, most commonly from colorectal cancer, and primary liver cancers that have metastasized are associated with poor outcomes. The underlying mechanisms by which the liver defends against these processes are largely unknown. Prohibitin 1 (PHB1) and methionine adenosyltransferase 1A (MAT1A) are highly expressed in the liver. They positively regulate each other and their deletion results in primary liver cancer. Here we investigated their roles in primary and secondary liver cancer metastasis.
METHODS: We identified common target genes of PHB1 and MAT1A using a metastasis array, and measured promoter activity and transcription factor binding using luciferase reporter assays and chromatin immunoprecipitation, respectively. We examined how PHB1 or MAT1A loss promotes liver cancer metastasis and whether their loss sensitizes to colorectal liver metastasis (CRLM).
RESULTS: Matrix metalloproteinase-7 (MMP-7) is a common target of MAT1A and PHB1 and its induction is responsible for increased migration and invasion when MAT1A or PHB1 is silenced. Mechanistically, PHB1 and MAT1A negatively regulate MMP7 promoter activity via an AP-1 site by repressing the MAFG-FOSB complex. Loss of MAT1A or PHB1 also increased MMP-7 in extracellular vesicles, which were internalized by colon and pancreatic cancer cells to enhance their oncogenicity. Low hepatic MAT1A or PHB1 expression sensitized to CRLM, but not if endogenous hepatic MMP-7 was knocked down first, which lowered CD4+ T cells while increasing CD8+ T cells in the tumor microenvironment. Hepatocytes co-cultured with colorectal cancer cells express less MAT1A/PHB1 but more MMP-7. Consistently, CRLM raised distant hepatocytes\' MMP-7 expression in mice and humans.
CONCLUSIONS: We have identified a PHB1/MAT1A-MAFG/FOSB-MMP-7 axis that controls primary liver cancer metastasis and sensitization to CRLM.
UNASSIGNED: Primary and secondary liver cancer metastasis is associated with poor outcomes but whether the liver has underlying defense mechanism(s) against metastasis is unknown. Here we examined the hypothesis that hepatic prohibitin 1 (PHB1) and methionine adenosyltransferase 1A (MAT1A) cooperate to defend the liver against metastasis. Our studies found PHB1 and MAT1A form a complex that suppresses matrix metalloproteinase-7 (MMP-7) at the transcriptional level and loss of either PHB1 or MAT1A sensitizes the liver to metastasis via MMP-7 induction. Strategies that target the PHB1/MAT1A-MMP-7 axis may be a promising approach for the treatment of primary and secondary liver cancer metastasis.

We investigated the utilities of the liver-to-psoas apparent diffusion coefficient ratios (LTPAR) yielded by diffusion-weighted magnetic resonance imaging (DWMRI) and the age-adjusted serum matrix metalloproteinase-7 (MMP-7) for the diagnosis of biliary atresia (BA) in cholestatic infants.
In total, 170 cholestatic infants were recruited, of whom 50 (29.41%) were diagnosed with BA after cholestatic workups. The LTPAR and MMP7 levels were assessed.
The LTPAR was significantly lower in BA infants, and the age-adjusted MMP7 ratio was significantly higher, compared to other cholestatic infants (both p < 0.001). Receiver operating characteristic curve analysis yielded a cutoff > 0.1 ng/mL.day for the age-adjusted MMP-7 ratio, and an LTPAR < 1.01 for the optimal prediction of BA (both p < 0.001). Univariate logistic regression analysis revealed that both an age-adjusted MMP-7 ratio > 0.1 ng/mL.day and an LTPAR < 1.01 were significant predictors of BA among cholestatic infants (odds ratio = 30.98 and 13.28; p < 0.001 and < 0.001, respectively). The significance of the age-adjusted MMP-7 ratio and the LTPAR persisted on multivariate logistic regression analysis after adjusting for sex and the serum gamma-glutamyl transferase level (p < 0.001 and < 0.001, respectively). The negative predictive values (NPVs) for BA were 91.49% and 94.17%, respectively, for the LTPAR and age-adjusted MMP-7 ratio.
The age-adjusted MMP-7 ratio and the LTPAR are both significant non-invasive predictors of BA. The consideration of both serum and imaging parameters may enhance BA diagnostic performance in cholestatic infants.

UNASSIGNED: The increase in mortality in rheumatoid arthritis (RA) patients with interstitial lung disease (ILD) is well known However, there are few studies on serum markers that can evaluate acute exacerbation or prognosis in RA-ILD patients The purpose of this study was to identify the association between biomarkers and lung lesions in patients with RA-ILD.
UNASSIGNED: We analyzed 153 patients with serum samples in a prospective, multicenter cohort of Korean RA-ILD patients The serum levels of biomarkers, matrix metalloproteinase (MMP-7), surfactant protein-D (SP-D), and Krebs von den Lungen-6 (KL-6) were measured and correlated with forced vital capacity (FVC), diffusing capacity for carbon monoxide (DLCO) and the results of computed tomography (CT) CT results were interpreted semi-quantitatively according to the extent of lung lesions (grade 1, 0%∼25%; grade 2, 26%∼50%; grade 3, 51%∼75%; grade 4, 76%∼100%).
UNASSIGNED: MMP-7, SP-D, and KL-6 were negatively correlated with FVC (MMP-7, r=-0267, p=0001; SP-D, r=-0250, p=0002; KL-6, r=-0223, p=0006) and DLCO (MMP-7, r=-0404, p<0001; SP-D, r=-0286, p=0001; KL-6, r=-0226, p=0007) In addition, MMP-7, SP-D, and KL-6 tended to increase with higher grades of lung lesions on CT (MMP-7, p=0013; SP-D, p<0001; KL-6, p<0001).
UNASSIGNED: MMP-7, SP-D, and KL-6 can be used to evaluate the functional and anatomical status of lung involvement in the RA-ILD patients.

The spread through air spaces (STAS) of adenocarcinoma (ADC) is a unique pattern for local invasion, which comprises the spread of tumor cells within air spaces beyond the tumor edge without a direct connection with the primary tumor. Matrix metalloproteinase-7 (MMP-7), a secreted proteolytic enzyme that degrades various extracellular matrix components and other substrates, regulates several pathophysiological processes as well as the occurrence and development of cancers in humans. Here, we retrospectively analyzed a cohort of Japanese patients with treatment-naive, surgically-resected lung ADC to assess whether MMP-7 is associated with STAS development and if it could be used as a predictor of STAS.
We performed histological evaluation using hematoxylin and eosin staining and immunohistochemical analysis using microarrays. Thereafter, we scored the examined tissues for immune markers to identify significant tumor STAS predictors.
We identified that high MMP-7 expression is an independent predictor of a high STAS incidence. Multivariate analysis revealed that MMP-7 expression was correlated with tumor behavior and poor prognosis. Furthermore, STAS remained significantly associated with a higher risk of ADC recurrence.
The development of tumor STAS could be promoted by the functioning of MMP-7. This study could be a crucial basis for future investigations on the detection of tumor STAS.

Matrix Metalloproteinases (MMPs) have been found to have important roles in vascular pathology and may be involved in the occurrence of pre-eclampsia. In this study, the serum levels of MMP-2, -7, -9 in normal pregnant women and pre-eclampsia patients were analyzed to assess their predictive value.
A total of 1563 pregnant women from Peking University Third Hospital, from February 2021 to October 2021, were enrolled. Serum samples were collected from patients one to three times, during the different trimesters. Among the 102 singleton pre-eclampsia patients, we collected samples from 33 patients in the first trimester (6-13 GW), 33 in the second trimester (14-28 GW), 41 in the third trimester (29-41 GW) and 28 after onset of pre-eclampsia. Samples from each trimester were collected before the onset of pre-eclampsia. Then we selected 35, 37, 43 and 25 samples from 124 healthy pregnant women by matching their age, BMI and gestational weeks, using these as the control groups. Serum levels of MMP-2, -7, -9 were detected by ELISA. The receiver operating characteristic (ROC) curve was used to evaluate their predictive value.
Except for the first trimester, MMP-2 and MMP-7 were significantly higher in the pre-eclampsia group (p < 0.5). Additionally, in the pre-eclampsia group, MMP-9 increased significantly in the first trimester and after the onset of pre-eclampsia but decreased significantly in the second and third trimesters (p < 0.5). The ROC curve indicated that MMP-9, MMP-2 and MMP-7 were the best indicators for predicting pre-eclampsia in the first, second and third trimesters, respectively.
Increased MMP-2 and MMP-7 levels and a decreased MMP-9 level seem to be related to the pathogenesis of pre-eclampsia and are expected to be potential predictors of pre-eclampsia.

OBJECTIVE: The aim of this study was to investigate the relationship between matrix metalloproteinase-7 (MMP-7) expression and the clinical and pathological characteristics of salivary adenoid cystic carcinomas (SACC) of the palatal minor salivary gland.
METHODS: In this study, 58 samples of SACC and 10 samples of normal salivary gland tissue were examined. Immunohistochemistry was used to detect MMP-7 and vascular endothelial growth factor A (VEGF-A) expression in SACC and normal tissues. The clinical and pathological characteristics of the patients with SACC were collected.
RESULTS: Of the 58 SACC samples, 44 were positive for MMP-7, and the expression rate was 75.9%. No expression was detected in the 10 normal salivary gland tissues. The level of MMP-7 expression in the SACC and normal samples was significantly different. The level of expression of MMP-7 in the SACC samples did not correlate with age, sex or pathological type but did correlate with pathological grade, nerve infiltration and clinical stage. There was a positive correlation between VEGF-A and MMP-7 expression.
CONCLUSIONS: The SACC samples showed high expression of MMP-7, which was associated with tumour differentiation, invasiveness and clinical stage. The detection of MMP-7 positively correlated with the detection of VEGF-A in SACC.