AIM: To investigate the expression of integrin αvβ6 and matrix metalloproteinase 9 (MMP-9), their association with prognostic factors and to assess their predictive role in gastric cancer patie...AIM: To investigate the expression of integrin αvβ6 and matrix metalloproteinase 9 (MMP-9), their association with prognostic factors and to assess their predictive role in gastric cancer patients.METHODS: Immunohistochemistry was used to determine the expressions of integrin αvβ6 and MMP-9 in 126 specimens from patients with primary gastric carcinoma. Associations between immunohistochemical staining and various clinic pathologic variables of tissue specimens were evaluated by the χ<sup>2</sup> test and Fisher’s exact test. Expression correlation of αvβ6 and MMP-9 was assessed using bivariate correlation analysis. The patients were followed-up every 3 mo in the first two years and at least every 6 mo afterwards, with a median follow-up of 56 mo (ranging from 2 mo to 94 mo). Four different combinations of αvβ6 and MMP-9 levels (that is, both markers positive, both markers negative, αvβ6 positive with MMP-9 negative, and αvβ6 negative with MMP-9 positive) were evaluated for their relative effect on survival. The difference in survival curves was evaluated with a log-rank test. Survival analysis was conducted using the Kaplan-Meier survival and Cox proportional hazards model analysis.RESULTS: The expressions of integrin αvβ6 and MMP-9 were investigated in 126 cases, among which 34.92% were positive for αvβ6 expression, and 42.06% for MMP-9 expression. The expression of αvβ6 was associated with Lauren type, differentiation, N stage, and TNM stage (the P values were 0.006, 0.038, 0.016, and 0.002, respectively). While MMP-9 expression was associated with differentiation, T stage, N stage, and TNM stage (the P values were 0.039, 0.014, 0.033, and 0.008, respectively). The positive correlation between αvβ6 and MMP-9 in gastric cancer was confirmed by a correlation analysis. The Kaplan-Meier survival analysis showed that patients with expression of αvβ6 or MMP-9 alone died earlier than those with negative expression and that patients who were both αvβ6 and MMP-9 positive had a shorter overall survival than those with the opposite pattern (both αvβ6 and MMP-9 negative) (P = 0.000). A Cox model indicated that positive expression of αvβ6 and MMP-9, diffuse Lauren type, as well as a senior grade of N stage, M stage, and TNM stage were predictors of a poor prognosis in univariate analysis. Only αvβ6 and MMP-9 retained their significance when adjustments were made for other known prognostic factors in multivariate analysis (RR = 2.632, P = 0.003 and RR = 1.813, P = 0.007).CONCLUSION: The expression of αvβ6 and MMP-9 are closely correlated, and the combinational pattern of αvβ6 and MMP-9 can serve as a more effective prognostic index for gastric cancer patients.展开更多
Objective： To investigate the clinic values of combining test of serum matrix metalloproteinase 9 （MMP-9）, acetyl heparinase （Hpa） and Cathepsin L （CL） in diagnosis of ovarian cancer. Methods： Serum levels of...Objective： To investigate the clinic values of combining test of serum matrix metalloproteinase 9 （MMP-9）, acetyl heparinase （Hpa） and Cathepsin L （CL） in diagnosis of ovarian cancer. Methods： Serum levels of MMP-9, Hpa and CL were detected in a total of 418 cases, including 217 cases with ovarian malignant tumor, 100 cases with ovarian benign tumor and 101 healthy controls, by using enzyme-linked immunosorbent assay （ELISA）. Their correlation with clinicopathologic feature of ovarian malignant tumor was analyzed and their diagnosis performance was evaluated by receiver operating characteristic （ROC）. The combined diagnosis model was established by logistic regression analysis. Results： The serum levels of MMP-9, Hpa and CL were significantly higher in patients with ovarian malignant tumor than in benign tumor and healthy control, the serum levels of CL and Hpa were higher in epithelial cancer than in non-epithelial tumor, and MMP-9, Hpa and CL were elevated in low grade and advanced stage compared to high grade and early stage. The sensitivity for diagnosis of ovarian malignant tumor from high to low was CL, Hpa and MMP-9, and the specificity was MMP-9, CL and Hpa. The united diagnosis model was established and showed the sensitivity and specificity of combined detection were 84.6% and 82.1%, respectively, which were significantly higher than a single tumor marker. Conclusion： Serum MMP-9, Hpa and CL were correlated with ovarian malignant tumor and the combined detection of which may be valuable for clinical diagnosis of ovarian malignant tumor.展开更多
Cervical and intracranial angioplasty and stenting is an effective and safe method of reducing the risk of ischemic stroke, but it may be affected by in-stent restenosis. The present study in-vestigated serum level of...Cervical and intracranial angioplasty and stenting is an effective and safe method of reducing the risk of ischemic stroke, but it may be affected by in-stent restenosis. The present study in-vestigated serum level of matrix metalloproteinase 9 as a predictor of restenosis after 40 patients underwent cervical and/or intracranial angioplasty and stenting. Results showed that resteno-sis occurred in 30% （3/10） of patients when the serum level of matrix metalloproteinase 9 at 3 days after surgery was 2.5 times higher than preoperative level. No restenosis occurred when the serum level of matrix metalloproteinase 9 at 3 days after surgery was not 2.5 times higher than preoperative level. Restenosis occurred in 12% （2/17） of patients when the serum level of matrix metalloproteinase 9 was higher than preoperative level for more than 30 days after surgery, but only occurred in 4% （1/23） of patients when the serum level of matrix metalloproteinase 9 was higher than preoperative level for less than 30 days after surgery. However, the differences observed were not statistically signiifcant （P 〉 0.05）. Experimental ifndings indicate that when the serum level of matrix metalloproteinase 9 is 2.5 times higher than preoperative level at 3 days after cervi-cal and intracranial angioplasty and stenting, it may serve as a predictor of in-stent restenosis.展开更多
To study the expression of matrix metalloproteinase 2 and 9 in human prostate cancer, matrix metalloproteinase 2 and 9 were immunohistochemically detected in tissues of prostate cancer and benign prostatic hype...To study the expression of matrix metalloproteinase 2 and 9 in human prostate cancer, matrix metalloproteinase 2 and 9 were immunohistochemically detected in tissues of prostate cancer and benign prostatic hyperplasia (BPH). Our results showed that matrix metalloproteinase 2 and 9 levels in prostate cancer were much higher than those in tissues of BPH, with the cancer invasion being positively correlated with the expression of the metalloproteinases. It is concluded that matrix metalloproteinase 2 and 9 are better molecular markers, which are of help in the diagnosis and prediction of prognosis of prostate cancer.展开更多
BACKGROUND The importance of the neuronal microenvironment has been recently highlighted in gut region-specific diabetic enteric neuropathy. Regionally distinct thickening of endothelial basement membrane(BM) of intes...BACKGROUND The importance of the neuronal microenvironment has been recently highlighted in gut region-specific diabetic enteric neuropathy. Regionally distinct thickening of endothelial basement membrane(BM) of intestinal capillaries supplying the myenteric ganglia coincide with neuronal damage in different intestinal segments. Accelerated synthesis of matrix molecules and reduced degradation of matrix components may also contribute to the imbalance of extracellular matrix dynamics resulting in BM thickening. Among the matrix degrading proteinases, matrix metalloproteinase 9(MMP9) and its tissue inhibitor(TIMP1) are essential in regulating extracellular matrix remodelling.AIM To evaluate the intestinal segment-specific effects of diabetes and insulin replacement on ganglionic BM thickness, MMP9 and TIMP1 expression.METHODS Ten weeks after the onset of hyperglycaemia gut segments were taken from the duodenum and ileum of streptozotocin-induced diabetic, insulin-treated diabetic and sex-and age-matched control rats. The thickness of BM surrounding myenteric ganglia was measured by electron microscopic morphometry. Wholemount preparations of myenteric plexus were prepared from the different gut regions for MMP9/TIMP1 double-labelling fluorescent immunohistochemistry. Post-embedding immunogold electron microscopy was applied on ultrathin sections to evaluate the MMP9 and TIMP1 expression in myenteric ganglia and their microenvironment from different gut segments and conditions. The MMP9 and TIMP1 messenger ribonucleic acid(m RNA) level was measured by quantitative polymerase chain reaction.RESULTS Ten weeks after the onset of hyperglycaemia, the ganglionic BM was significantly thickened in the diabetic ileum, while it remained intact in the duodenum. The immediate insulin treatment prevented the diabetes-related thickening of the BM surrounding the ileal myenteric ganglia. Quantification of particle density showed an increasing tendency for MMP9 and a decreasing tendency for TIMP1 from the proximal to the distal small intestine under control conditions. In the diabetic ileum, the number of MMP9-indicating gold particles decreased in myenteric ganglia, endothelial cells of capillaries and intestinal smooth muscle cells, however, it remained unchanged in all duodenal compartments. The MMP9/TIMP1 ratio was also decreased in ileal ganglia only. However, a marked segment-specific induction was revealed in MMP9 and TIMP1 at the m RNA levels.CONCLUSION These findings support that the regional decrease in MMP9 expression in myenteric ganglia and their microenvironment may contribute to extracellular matrix accumulation, resulting in a region-specific thickening of ganglionic BM.展开更多
BACKGROUND Prostate cancer(PC)is one of the most common malignant tumors in men,and bone metastasis is one of its common complications,which seriously affects the quality of life and prognosis of patients.AIM To inves...BACKGROUND Prostate cancer(PC)is one of the most common malignant tumors in men,and bone metastasis is one of its common complications,which seriously affects the quality of life and prognosis of patients.AIM To investigate the diagnostic value of technetium-99m-methylene diphosphonate(99mTc-MDP)single photon emission computed tomography(SPECT)/CT imaging combined with the serum prostate-specific antigen(PSA)/free PSA ratio for PC bone metastasis(PCBM).METHODS One hundred patients with PC who visited the Hospital of Chengdu University of Traditional Chinese Medicine from January 2020 to January 2022 were recruited as the experimental(Exp)group,while 30 patients with benign prostatic lesions(BPLs)were recruited as the control(Ctrl)group.All patients underwent 99mTc-MDP SPECT/CT imaging and serum PSA/fPSA testing.The SPECT/CT imaging results and serum PSA/fPSA ratios of patients were analyzed to evaluate their diagnostic values for PCBM.RESULTS The difference in general information of the patients was not obvious,showing comparability.The two methods showed no visible differences in negative predictive value and sensitivity for patients with PCBM,but had great differences in positive predictive value and specificity(P<0.05).The PSA/fPSA ratio of patients with PC in the Exp group was lower than those with BPLs,and patients with PCBM had a much lower PSA/fPSA ratio than those without PC(P<0.05).The results confirmed that the combined use of 99mTc-MDP SPECT/CT imaging and serum PSA/fPSA ratio achieved a detection rate of 95%for PCBM.CONCLUSION The combination of 99mTc-MDP SPECT/CT and PSA/fPSA ratio is accurate and reliable for the diagnosis of PCBM,which provides an important reference for clinical practice.展开更多
The relationship between angiogenesis and eukaryotic translation initiation factor 4E （EIF4E） expression level in non Hodgkin lymphoma （NHL） was studied. Mean microvessel density （MVD） and EIF4E were detected in...The relationship between angiogenesis and eukaryotic translation initiation factor 4E （EIF4E） expression level in non Hodgkin lymphoma （NHL） was studied. Mean microvessel density （MVD） and EIF4E were detected in 52 lymph node samples paraffin sections of patients with newly diagnosed NHL by the way of immunohistochemistry. Antisense EIF4E cDNA was cloned into plasmid pcDNA3.1 （＋） and transfected into Raji cells. A series of angiogenesis related factors,including vascular endothelial growth factor （VEGF）, matrix metalloproteinases 9 （MMP-9） and tissue inhibitor of metalloproteinases-2 （TIMP-2） proteins were detected by Western blot. The results showed that： （1） The Expression of EIF4E and MVD was higher in aggressive lymphomas than in indolent lymphomas（P〈0.05）and the expression of EIF4E was positively correlated with MVD in lymph node of NHL（r=0. 695, P〈0.01）. （2） Antisense EIF4E eukaryocytic expression vector （pcDNA3. 1-EIF4Eas） was constructed successfully. （3） EIF4E, VEGF and MMP-9 were expressed at high levels in Raji cells as compared to normal human peripheral blood monocular cells （NHPMC）, and blockage of EIF4E expression brought down the expression of VEGF and MMP-9. However, TIMP-2 was undetectable in Rail cells, although a moderate level of TIMP-2 was detected in NHPMC. It was concluded that the increased EIF4E expression was associated with aggressive property of NHL.展开更多
BACKGROUND: The high level of matrix metalloproteinase 9(MMP9) is thought to slow down the healing of diabetic foot ulcers. Whether it can influence the biological behaviors of skin fi broblasts and affect wound heali...BACKGROUND: The high level of matrix metalloproteinase 9(MMP9) is thought to slow down the healing of diabetic foot ulcers. Whether it can influence the biological behaviors of skin fi broblasts and affect wound healing is still unclear. The present study aimed to observe changes in the biological behaviors of rat dermal fi broblasts induced by high expression of MMP9 and to clarify the possible mechanisms of wound healing for diabetic foot.METHODS: A cell model of skin f ibroblast with high expression of MMP9 was established by coculture of high glucose(22.0 mmol/L) and homocysteine(100 μmol/L). A control group was incubated with normal glucose(5.5 mmol/L). Realtime PCR, ELISA and gelatin zymography were used to detect the MMP9 mRNA, protein expression and activity of MMP9. Flow cytometry, CCK-8, ELISA assay, scratch test and transwell were used to detect cell proliferation, viability, collagen(hydroxyproline) secretion, horizontal migration and vertical migration of cells. The data were expressed as mean±SD. P value less than 0.05 was considered statistically signif icant.RESULTS: The expression of MMP9 mRNA, protein levels and the activity of MMP9 were much higher in the high MMP9 group than in the control group(7.05±1.02 vs. 1.00±0.00, 206.9±33.6 pg/mL vs. 40.4±5.9 pg/mL, and 1.47±0.13 vs. 0.57±0.12, respectively, P<0.01). The proportion of S-phase cells, proliferation index, cell viability, collagen(hydroxyproline) secretion, horizontal migration rate and the number of vertical migration cells were lower in the high MMP9 group than in the control group(P<0.01).CONCLUSION: Fibroblasts with a high expression of MMP9 decreased proliferation, activity, secretion and migration of collagens, suggesting that MMP9 may inhibit the biological behaviors of fi broblasts.展开更多
OBJECTIVE:To explore whether the regulation of matrix metalloproteinase 9(MMP-9)/tissue inhibitors of MMPs(TIMPs)gene expression through histone acetylation is a possible mechanism by which electroacupuncture(EA)prote...OBJECTIVE:To explore whether the regulation of matrix metalloproteinase 9(MMP-9)/tissue inhibitors of MMPs(TIMPs)gene expression through histone acetylation is a possible mechanism by which electroacupuncture(EA)protects blood-brain barrier(BBB)integrity in a middle cerebral artery occlusion(MCAO)rat model.METHODS:Male Sprague-Dawley rats were divided into four groups:the sham group,the MCAO group,the MCAO+EA(MEA)group,and the MCAO+EA+HAT inhibitor(HATi)group.The MCAO model was generated by blocking the middle cerebral artery.EA was applied to Baihui(GV20).Samples were collected 1 or 3 d after reperfusion.Neurological function scores and Evans blue extravasation were employed to evaluate the poststroke injury.The effect of EA on MMP-9/TIMPs gene expression was assessed by real-time fluorescence quantitative polymerase chain reaction(RT-qPCR)and chromatin immunoprecipitation(ChIP).RESULTS:Our results showed that EA treatment prominently improved neurological function and ameliorated BBB disruption.The RT-qPCR assay showed that EA reduced the expression of MMP-9 and promoted TIMP-2 mRNA expression,but HATi reversed these effects of EA.In addition,ChIP results revealed that EA decreased the enrichment of H3K9ace/H3K27ace at MMP-9 promoters and notably stimulated the recruitment of H3K9ace/H3K27ace at TIMP-2 promoter.CONCLUSION:EA treatment at Baihui(GV20)regulates the transcription of MMP-9 and TIMP-2 through histone acetylation modification in the acute stage of stroke,which preserves the structural integrity of the BBB in MCAO rats.These findings suggested that the histone acetylation-mediated transcriptional activity of target genes may be a crucial mechanism of EA treatment in stroke.展开更多
Dry eye disease(DED),primarily classified as multifactorial ocular surface disorder,afflicts tens of millions of individuals worldwide,adversely impacting their quality of life.Extensive research has been conducted on...Dry eye disease(DED),primarily classified as multifactorial ocular surface disorder,afflicts tens of millions of individuals worldwide,adversely impacting their quality of life.Extensive research has been conducted on tear film analysis over the past decades,offering a range of tests to evaluate its volume,health,and integrity.Yet,early diagnosis and effective treatment for DED continue to pose significant challenges in clinical settings.Nevertheless,by recognizing key phenomena in DED such as ocular surface inflammation,hyperosmolarity,and tear film instability,this article provides a comprehensive overview of both traditional and recently developed methods for diagnosing and monitoring DED.The information serves as a valuable resource not only for clinical diagnosis but also for further research into DED.展开更多
The long suspicion of the potential harm of carbon dioxide （CO2） pneumoperitoneum exists in laparoscopic cancer surgery. For better understanding of this problem, we targeted this study at the effects of CO2 pneumop...The long suspicion of the potential harm of carbon dioxide （CO2） pneumoperitoneum exists in laparoscopic cancer surgery. For better understanding of this problem, we targeted this study at the effects of CO2 pneumoperitoneum on the invasive ability of ovarian carcinoma cell line and the possible mechanism within it. To study the effects of CO2 pneumoperitoneum on carcinoma cell, SKOV3 cells were divided into 2 groups, respectively exposed to pneumoperitoneal CO2-insuffiation and normal conditions. To study the possible mechanism, SKOV3 cells were divided into 3 groups, one was exposed to CO2 pneumoperitoneum, one to N2 and the other to normal conditions served as control. The in vitro adhesive and invasive ability of the cells was analyzed through 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyl tetrazolium bromide （MTT） assay and Boyden filters metastasis model; the expressions of vascular endothelial growth factor C （VEGF-C） and matrix metalloproteinase 9 （MMP9） were determined by reverse transcription polymerase chain reaction（RT-PCR）, and Western blot. We found that the adhesive ratio of SKOV3 cells exposed to CO2 was significantly higher than that of the control group; cells exposed to CO2 invaded the matrigel with a greater number （P〈0.01）; the expression of VEGF-C exposed to both CO2 and N2 was significantly increased compared with control group （P〈0.05）; the MMP9 expression level of CO2 group was higher than that of N2 group, P〈0.05. We concluded that carbon dioxide pneumoperitoneum may improve the adhesive and invasive ability of ovarian carcinoma cell line in vitro and CO2 can also be an independent factor to stimulate the expression of MMP9.展开更多
Objective： The aim of this study was to investigate the expression of CD147 and matrix metalioprpteinsae 9 （MMP-9） in children with non-Hodgkin＇s lymphoma （NHL） and the relations between expressions of CD147 ＆ ...Objective： The aim of this study was to investigate the expression of CD147 and matrix metalioprpteinsae 9 （MMP-9） in children with non-Hodgkin＇s lymphoma （NHL） and the relations between expressions of CD147 ＆ MMP-9 and the clinical indexes. Methods： Specimens excised from NHL patients were prepared. Expression of CD147 and MMP-9 were tested by SABC immunohistochemistry and its correlation to clinical results were analyzed in this report. Results： The positive rate of CD147 expression was 73% （45/62）, and that of MMP-9 expression was 81% （50/62）. There was a positive correlation between CD147 and MMP-9 expressions. CD147 expression intensity was linked to clinical myelo-infiltration, tumor size, LDH value, and clinical staging （P 〈 0.05）, rather than children age, gender, or immune typing （P 〉 0.05）; MMP-9 expression intensity was linked to myelo-infiltration, and clinical staging （P 〈 0.05）, rather than age, gender, immune typing, tumor size, or LDH value （P 〉 0.05）. Five-year survival rates were 78% （22/28） and 45% （15/34） in CD147 （-）-（＋） and （＋＋）-（＋＋＋） cases respectively, and those were 84% （21/25） and 43% （16/37） in MMP-9 （-）-（＋） and （＋＋）-（＋＋＋） cases respectively, the difference was significant. Conclusion： The elevated expression of CD147 and/or MMP-9 correlates with a poor clinical outcome in patients with NHL.展开更多
Background Inflammation within vulnerable coronary plaques may cause unstable angina by promoting rupture and erosion. C-reactive protein （CRP） is the most reliable and accessible test method for clinical use for id...Background Inflammation within vulnerable coronary plaques may cause unstable angina by promoting rupture and erosion. C-reactive protein （CRP） is the most reliable and accessible test method for clinical use for identifying coronary artery disease event. Matrix metalloproteinase 9 （MMP-9） is highly over-expressed in the vulnerable regions of a plaque. Our aim was to evaluate the plasma levels of MMP-9 and hsCRP in subjects with both unstable angina and coronary plaques, as well as in those with unstable angina without coronary plaques.展开更多
Background Neuroprotective strategies following cardiopulmonary resuscitation （CPR） are an important focus in emergency and critical care medicine. Matrix metalloproteinases （MMPs）, especially MMP9 attracted much ...Background Neuroprotective strategies following cardiopulmonary resuscitation （CPR） are an important focus in emergency and critical care medicine. Matrix metalloproteinases （MMPs）, especially MMP9 attracted much attention because of its function in focal brain ischemia/reperfusion injury. In the focal cerebral ischemia model in rats, SB-3CT can suppress the expression of MMP9, relieving brain edema, and there was no studies on global cerebral ischemiareperfusion injury after CPR. Methods One hundred and twenty rats were randomly assigned to sham-operated （n=40）, resuscitation treatment （n=40）, and resuscitation control （n= 40） groups. Sham-operated group rats were anesthetized only and intubated tracheally, while the resuscitation treatment and resuscitation control groups also received cardiac arrest by asphyxiation, In the resuscitation treatment group, SB-3CT was injected intraperitoneally after restoring spontaneous circulation （ROSC）, defined as restoration of supraventricular rhythm and mean arterial pressure （MAP） 〉 60 mm Hg for more than 5 minutes. The resuscitation control group also implemented ROSC without injection of SB-3CT. The rats were executed and samples were taken immediately after death, then at 3, 9, 24, and 48 hours （n=-8）. Brain tissue expression of MMP9 protein, MMP9 mRNA, water content, Evans blue content, TNF-α, IL-1, and IL-6 was measured, and the brain tissue ultramicrostructure studied with electron microscopy. Results In the resuscitation control group, brain tissue expression of MMP9 protein and mRNA, water content, Evans blue content, TNF-α, IL-1, and IL-6 were significantly elevated at 3 hours, and peaked at 24 hours after resuscitation, when compared with the sham-operated group （P 〈0.05）. 1issue ultramicrostructure also changed in the resuscitation control group. By contrast, although all these indexes were increased in the resuscitation treatment group compared with the sham-operated group （P 〈0.05）, they were lower than in the resuscitation control group （P 〈0.05）. Conclusions Expression of MMP9 protein and mRNA, water content, Evans blue content, TNF-α, IL-1, and IL-6 increased in rat brain tissue after CPR, indicating disruption of the blood-brain barrier and excess inflammatory reaction. MMP9 expression was reduced with SB-3CT, resulting in reduced brain injury.展开更多
OBJECTIVE: To explore the effects of Taohong Siwu decoction(桃红四物汤, THSWD) on the extracellular matrix of endometrium in rats following drug-induced abortion.METHODS: Thirty-six pregnant female rats were administe...OBJECTIVE: To explore the effects of Taohong Siwu decoction(桃红四物汤, THSWD) on the extracellular matrix of endometrium in rats following drug-induced abortion.METHODS: Thirty-six pregnant female rats were administered mifepristone and misoprostol to induce abortion, and amounts of uterine bleeding were recorded. Pathological damage and collagen accumulation were detected by hematoxylin-eosin staining and Masson’s trichrome staining in uterus, respectively. Myeloperoxidase was evaluated by immunohistochemistry.The expression levels of fibronectin, laminin, matrix metalloproteinase 9(MMP-9), and tissue inhibitor of metalloproteinase 1(TIMP-1) were quantified using western blotting.RESULTS: THSWD could promote endometrial protection in rats following drug-induced abortion.The contents of cellulose and myeloperoxidase were significantly decreased in uterine tissue of THSWD-treated groups. Moreover, THSWD significantly decreased the expression levels of fibronectin, laminin, and TIMP-1. THSWD also significantly increased MMP-9 expression and the MMP-9/TIMP-1 ratio.CONCLUSION: THSWD plays a critical role in endometrial protection by reducing extracellular matrix deposition and uterine fibrosis. These effects may have been achieved by increasing MMP-9, reducing TIMP-1, and/or altering the ratio of MMP-9/TIMP-1.展开更多
基金Supported by China Postdoctoral Science Foundation funded Project,No.20080441310 and 201003781the Natural Science Foundation of China,No.81302123
文摘AIM: To investigate the expression of integrin αvβ6 and matrix metalloproteinase 9 (MMP-9), their association with prognostic factors and to assess their predictive role in gastric cancer patients.METHODS: Immunohistochemistry was used to determine the expressions of integrin αvβ6 and MMP-9 in 126 specimens from patients with primary gastric carcinoma. Associations between immunohistochemical staining and various clinic pathologic variables of tissue specimens were evaluated by the χ<sup>2</sup> test and Fisher’s exact test. Expression correlation of αvβ6 and MMP-9 was assessed using bivariate correlation analysis. The patients were followed-up every 3 mo in the first two years and at least every 6 mo afterwards, with a median follow-up of 56 mo (ranging from 2 mo to 94 mo). Four different combinations of αvβ6 and MMP-9 levels (that is, both markers positive, both markers negative, αvβ6 positive with MMP-9 negative, and αvβ6 negative with MMP-9 positive) were evaluated for their relative effect on survival. The difference in survival curves was evaluated with a log-rank test. Survival analysis was conducted using the Kaplan-Meier survival and Cox proportional hazards model analysis.RESULTS: The expressions of integrin αvβ6 and MMP-9 were investigated in 126 cases, among which 34.92% were positive for αvβ6 expression, and 42.06% for MMP-9 expression. The expression of αvβ6 was associated with Lauren type, differentiation, N stage, and TNM stage (the P values were 0.006, 0.038, 0.016, and 0.002, respectively). While MMP-9 expression was associated with differentiation, T stage, N stage, and TNM stage (the P values were 0.039, 0.014, 0.033, and 0.008, respectively). The positive correlation between αvβ6 and MMP-9 in gastric cancer was confirmed by a correlation analysis. The Kaplan-Meier survival analysis showed that patients with expression of αvβ6 or MMP-9 alone died earlier than those with negative expression and that patients who were both αvβ6 and MMP-9 positive had a shorter overall survival than those with the opposite pattern (both αvβ6 and MMP-9 negative) (P = 0.000). A Cox model indicated that positive expression of αvβ6 and MMP-9, diffuse Lauren type, as well as a senior grade of N stage, M stage, and TNM stage were predictors of a poor prognosis in univariate analysis. Only αvβ6 and MMP-9 retained their significance when adjustments were made for other known prognostic factors in multivariate analysis (RR = 2.632, P = 0.003 and RR = 1.813, P = 0.007).CONCLUSION: The expression of αvβ6 and MMP-9 are closely correlated, and the combinational pattern of αvβ6 and MMP-9 can serve as a more effective prognostic index for gastric cancer patients.
基金supported by a grant from the Provincial Research Project Funding of Guangxi,China (No. GSR 9817101)
文摘Objective： To investigate the clinic values of combining test of serum matrix metalloproteinase 9 （MMP-9）, acetyl heparinase （Hpa） and Cathepsin L （CL） in diagnosis of ovarian cancer. Methods： Serum levels of MMP-9, Hpa and CL were detected in a total of 418 cases, including 217 cases with ovarian malignant tumor, 100 cases with ovarian benign tumor and 101 healthy controls, by using enzyme-linked immunosorbent assay （ELISA）. Their correlation with clinicopathologic feature of ovarian malignant tumor was analyzed and their diagnosis performance was evaluated by receiver operating characteristic （ROC）. The combined diagnosis model was established by logistic regression analysis. Results： The serum levels of MMP-9, Hpa and CL were significantly higher in patients with ovarian malignant tumor than in benign tumor and healthy control, the serum levels of CL and Hpa were higher in epithelial cancer than in non-epithelial tumor, and MMP-9, Hpa and CL were elevated in low grade and advanced stage compared to high grade and early stage. The sensitivity for diagnosis of ovarian malignant tumor from high to low was CL, Hpa and MMP-9, and the specificity was MMP-9, CL and Hpa. The united diagnosis model was established and showed the sensitivity and specificity of combined detection were 84.6% and 82.1%, respectively, which were significantly higher than a single tumor marker. Conclusion： Serum MMP-9, Hpa and CL were correlated with ovarian malignant tumor and the combined detection of which may be valuable for clinical diagnosis of ovarian malignant tumor.
基金supported by the Fund for Distinguished Young Doctors from Fujian Provincial Health Department,No.2011-1-7
文摘Cervical and intracranial angioplasty and stenting is an effective and safe method of reducing the risk of ischemic stroke, but it may be affected by in-stent restenosis. The present study in-vestigated serum level of matrix metalloproteinase 9 as a predictor of restenosis after 40 patients underwent cervical and/or intracranial angioplasty and stenting. Results showed that resteno-sis occurred in 30% （3/10） of patients when the serum level of matrix metalloproteinase 9 at 3 days after surgery was 2.5 times higher than preoperative level. No restenosis occurred when the serum level of matrix metalloproteinase 9 at 3 days after surgery was not 2.5 times higher than preoperative level. Restenosis occurred in 12% （2/17） of patients when the serum level of matrix metalloproteinase 9 was higher than preoperative level for more than 30 days after surgery, but only occurred in 4% （1/23） of patients when the serum level of matrix metalloproteinase 9 was higher than preoperative level for less than 30 days after surgery. However, the differences observed were not statistically signiifcant （P 〉 0.05）. Experimental ifndings indicate that when the serum level of matrix metalloproteinase 9 is 2.5 times higher than preoperative level at 3 days after cervi-cal and intracranial angioplasty and stenting, it may serve as a predictor of in-stent restenosis.
文摘To study the expression of matrix metalloproteinase 2 and 9 in human prostate cancer, matrix metalloproteinase 2 and 9 were immunohistochemically detected in tissues of prostate cancer and benign prostatic hyperplasia (BPH). Our results showed that matrix metalloproteinase 2 and 9 levels in prostate cancer were much higher than those in tissues of BPH, with the cancer invasion being positively correlated with the expression of the metalloproteinases. It is concluded that matrix metalloproteinase 2 and 9 are better molecular markers, which are of help in the diagnosis and prediction of prognosis of prostate cancer.
基金European Union and the Hungarian Government in the framework,No.EFOP-3.6.1-16-2016-00008Hungarian NKFIH fund project,No.FK131789(to Bódi N)+1 种基金János Bolyai Research Scholarship of the Hungarian Academy of Sciences(to Bódi N)and New National Excellence Program of the Ministry for Innovation and Technology from the source of the National Research,Development and Innovation Fund,No.ÚNKP-20-5(to Bódi N).
文摘BACKGROUND The importance of the neuronal microenvironment has been recently highlighted in gut region-specific diabetic enteric neuropathy. Regionally distinct thickening of endothelial basement membrane(BM) of intestinal capillaries supplying the myenteric ganglia coincide with neuronal damage in different intestinal segments. Accelerated synthesis of matrix molecules and reduced degradation of matrix components may also contribute to the imbalance of extracellular matrix dynamics resulting in BM thickening. Among the matrix degrading proteinases, matrix metalloproteinase 9(MMP9) and its tissue inhibitor(TIMP1) are essential in regulating extracellular matrix remodelling.AIM To evaluate the intestinal segment-specific effects of diabetes and insulin replacement on ganglionic BM thickness, MMP9 and TIMP1 expression.METHODS Ten weeks after the onset of hyperglycaemia gut segments were taken from the duodenum and ileum of streptozotocin-induced diabetic, insulin-treated diabetic and sex-and age-matched control rats. The thickness of BM surrounding myenteric ganglia was measured by electron microscopic morphometry. Wholemount preparations of myenteric plexus were prepared from the different gut regions for MMP9/TIMP1 double-labelling fluorescent immunohistochemistry. Post-embedding immunogold electron microscopy was applied on ultrathin sections to evaluate the MMP9 and TIMP1 expression in myenteric ganglia and their microenvironment from different gut segments and conditions. The MMP9 and TIMP1 messenger ribonucleic acid(m RNA) level was measured by quantitative polymerase chain reaction.RESULTS Ten weeks after the onset of hyperglycaemia, the ganglionic BM was significantly thickened in the diabetic ileum, while it remained intact in the duodenum. The immediate insulin treatment prevented the diabetes-related thickening of the BM surrounding the ileal myenteric ganglia. Quantification of particle density showed an increasing tendency for MMP9 and a decreasing tendency for TIMP1 from the proximal to the distal small intestine under control conditions. In the diabetic ileum, the number of MMP9-indicating gold particles decreased in myenteric ganglia, endothelial cells of capillaries and intestinal smooth muscle cells, however, it remained unchanged in all duodenal compartments. The MMP9/TIMP1 ratio was also decreased in ileal ganglia only. However, a marked segment-specific induction was revealed in MMP9 and TIMP1 at the m RNA levels.CONCLUSION These findings support that the regional decrease in MMP9 expression in myenteric ganglia and their microenvironment may contribute to extracellular matrix accumulation, resulting in a region-specific thickening of ganglionic BM.
文摘BACKGROUND Prostate cancer(PC)is one of the most common malignant tumors in men,and bone metastasis is one of its common complications,which seriously affects the quality of life and prognosis of patients.AIM To investigate the diagnostic value of technetium-99m-methylene diphosphonate(99mTc-MDP)single photon emission computed tomography(SPECT)/CT imaging combined with the serum prostate-specific antigen(PSA)/free PSA ratio for PC bone metastasis(PCBM).METHODS One hundred patients with PC who visited the Hospital of Chengdu University of Traditional Chinese Medicine from January 2020 to January 2022 were recruited as the experimental(Exp)group,while 30 patients with benign prostatic lesions(BPLs)were recruited as the control(Ctrl)group.All patients underwent 99mTc-MDP SPECT/CT imaging and serum PSA/fPSA testing.The SPECT/CT imaging results and serum PSA/fPSA ratios of patients were analyzed to evaluate their diagnostic values for PCBM.RESULTS The difference in general information of the patients was not obvious,showing comparability.The two methods showed no visible differences in negative predictive value and sensitivity for patients with PCBM,but had great differences in positive predictive value and specificity(P<0.05).The PSA/fPSA ratio of patients with PC in the Exp group was lower than those with BPLs,and patients with PCBM had a much lower PSA/fPSA ratio than those without PC(P<0.05).The results confirmed that the combined use of 99mTc-MDP SPECT/CT imaging and serum PSA/fPSA ratio achieved a detection rate of 95%for PCBM.CONCLUSION The combination of 99mTc-MDP SPECT/CT and PSA/fPSA ratio is accurate and reliable for the diagnosis of PCBM,which provides an important reference for clinical practice.
文摘The relationship between angiogenesis and eukaryotic translation initiation factor 4E （EIF4E） expression level in non Hodgkin lymphoma （NHL） was studied. Mean microvessel density （MVD） and EIF4E were detected in 52 lymph node samples paraffin sections of patients with newly diagnosed NHL by the way of immunohistochemistry. Antisense EIF4E cDNA was cloned into plasmid pcDNA3.1 （＋） and transfected into Raji cells. A series of angiogenesis related factors,including vascular endothelial growth factor （VEGF）, matrix metalloproteinases 9 （MMP-9） and tissue inhibitor of metalloproteinases-2 （TIMP-2） proteins were detected by Western blot. The results showed that： （1） The Expression of EIF4E and MVD was higher in aggressive lymphomas than in indolent lymphomas（P〈0.05）and the expression of EIF4E was positively correlated with MVD in lymph node of NHL（r=0. 695, P〈0.01）. （2） Antisense EIF4E eukaryocytic expression vector （pcDNA3. 1-EIF4Eas） was constructed successfully. （3） EIF4E, VEGF and MMP-9 were expressed at high levels in Raji cells as compared to normal human peripheral blood monocular cells （NHPMC）, and blockage of EIF4E expression brought down the expression of VEGF and MMP-9. However, TIMP-2 was undetectable in Rail cells, although a moderate level of TIMP-2 was detected in NHPMC. It was concluded that the increased EIF4E expression was associated with aggressive property of NHL.
基金supported by grants from the National Natural Science Foundation of China(81070660)the Science and Technology Project Foundation of Guangdong Province(2008A030201012)+1 种基金Medical Science and Technology Research Foundation of Guangdong Province(A2012183)the Science and Technology Project Foundation of Guangdong Province(2009B091300128)
文摘BACKGROUND: The high level of matrix metalloproteinase 9(MMP9) is thought to slow down the healing of diabetic foot ulcers. Whether it can influence the biological behaviors of skin fi broblasts and affect wound healing is still unclear. The present study aimed to observe changes in the biological behaviors of rat dermal fi broblasts induced by high expression of MMP9 and to clarify the possible mechanisms of wound healing for diabetic foot.METHODS: A cell model of skin f ibroblast with high expression of MMP9 was established by coculture of high glucose(22.0 mmol/L) and homocysteine(100 μmol/L). A control group was incubated with normal glucose(5.5 mmol/L). Realtime PCR, ELISA and gelatin zymography were used to detect the MMP9 mRNA, protein expression and activity of MMP9. Flow cytometry, CCK-8, ELISA assay, scratch test and transwell were used to detect cell proliferation, viability, collagen(hydroxyproline) secretion, horizontal migration and vertical migration of cells. The data were expressed as mean±SD. P value less than 0.05 was considered statistically signif icant.RESULTS: The expression of MMP9 mRNA, protein levels and the activity of MMP9 were much higher in the high MMP9 group than in the control group(7.05±1.02 vs. 1.00±0.00, 206.9±33.6 pg/mL vs. 40.4±5.9 pg/mL, and 1.47±0.13 vs. 0.57±0.12, respectively, P<0.01). The proportion of S-phase cells, proliferation index, cell viability, collagen(hydroxyproline) secretion, horizontal migration rate and the number of vertical migration cells were lower in the high MMP9 group than in the control group(P<0.01).CONCLUSION: Fibroblasts with a high expression of MMP9 decreased proliferation, activity, secretion and migration of collagens, suggesting that MMP9 may inhibit the biological behaviors of fi broblasts.
基金the National Natural Science Foundation of China:the Role of Intestinal Flora-Treg/γδT Cell-IL-17 Signaling in the Neuroprotective Effect of Electroacupuncture on Ischemic Brain Injury(No.81774403)the Natural Science Foundation of the Jiangsu Province of China:Study on the Mechanism of Acupuncture Antistroke Immune Inflammatory Response Based on Intestinal Treg/γδT Cell-IL-17 Signaling Pathway(No.BK20171492)+2 种基金the Postgraduate Scientific Research Innovation Practice Project of the Jiangsu Province of China:a Study based on the Butyric Acid-HDAC-Foxp3 Pathway to Explore the Regulatory Effect of Acupuncture on Intestinal Treg in Rats with Stroke(No.KYCX21_1715)a Study on the Anti-brain Injury of Electroacupuncture Based on Intestinal Microbiota-Treg/γδT Cell-IL-17 Pathway(No.KYCX21_1716)the Key University Science Research Project of Jiangsu Province:the Role of Preactivation of the Treg Immune Response in the Mechanism of Anti-stroke Neuroinflammatory Response in Acupuncture Pretreatment(No.22KJA360003)。
文摘OBJECTIVE:To explore whether the regulation of matrix metalloproteinase 9(MMP-9)/tissue inhibitors of MMPs(TIMPs)gene expression through histone acetylation is a possible mechanism by which electroacupuncture(EA)protects blood-brain barrier(BBB)integrity in a middle cerebral artery occlusion(MCAO)rat model.METHODS:Male Sprague-Dawley rats were divided into four groups:the sham group,the MCAO group,the MCAO+EA(MEA)group,and the MCAO+EA+HAT inhibitor(HATi)group.The MCAO model was generated by blocking the middle cerebral artery.EA was applied to Baihui(GV20).Samples were collected 1 or 3 d after reperfusion.Neurological function scores and Evans blue extravasation were employed to evaluate the poststroke injury.The effect of EA on MMP-9/TIMPs gene expression was assessed by real-time fluorescence quantitative polymerase chain reaction(RT-qPCR)and chromatin immunoprecipitation(ChIP).RESULTS:Our results showed that EA treatment prominently improved neurological function and ameliorated BBB disruption.The RT-qPCR assay showed that EA reduced the expression of MMP-9 and promoted TIMP-2 mRNA expression,but HATi reversed these effects of EA.In addition,ChIP results revealed that EA decreased the enrichment of H3K9ace/H3K27ace at MMP-9 promoters and notably stimulated the recruitment of H3K9ace/H3K27ace at TIMP-2 promoter.CONCLUSION:EA treatment at Baihui(GV20)regulates the transcription of MMP-9 and TIMP-2 through histone acetylation modification in the acute stage of stroke,which preserves the structural integrity of the BBB in MCAO rats.These findings suggested that the histone acetylation-mediated transcriptional activity of target genes may be a crucial mechanism of EA treatment in stroke.
文摘Dry eye disease(DED),primarily classified as multifactorial ocular surface disorder,afflicts tens of millions of individuals worldwide,adversely impacting their quality of life.Extensive research has been conducted on tear film analysis over the past decades,offering a range of tests to evaluate its volume,health,and integrity.Yet,early diagnosis and effective treatment for DED continue to pose significant challenges in clinical settings.Nevertheless,by recognizing key phenomena in DED such as ocular surface inflammation,hyperosmolarity,and tear film instability,this article provides a comprehensive overview of both traditional and recently developed methods for diagnosing and monitoring DED.The information serves as a valuable resource not only for clinical diagnosis but also for further research into DED.
文摘The long suspicion of the potential harm of carbon dioxide （CO2） pneumoperitoneum exists in laparoscopic cancer surgery. For better understanding of this problem, we targeted this study at the effects of CO2 pneumoperitoneum on the invasive ability of ovarian carcinoma cell line and the possible mechanism within it. To study the effects of CO2 pneumoperitoneum on carcinoma cell, SKOV3 cells were divided into 2 groups, respectively exposed to pneumoperitoneal CO2-insuffiation and normal conditions. To study the possible mechanism, SKOV3 cells were divided into 3 groups, one was exposed to CO2 pneumoperitoneum, one to N2 and the other to normal conditions served as control. The in vitro adhesive and invasive ability of the cells was analyzed through 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyl tetrazolium bromide （MTT） assay and Boyden filters metastasis model; the expressions of vascular endothelial growth factor C （VEGF-C） and matrix metalloproteinase 9 （MMP9） were determined by reverse transcription polymerase chain reaction（RT-PCR）, and Western blot. We found that the adhesive ratio of SKOV3 cells exposed to CO2 was significantly higher than that of the control group; cells exposed to CO2 invaded the matrigel with a greater number （P〈0.01）; the expression of VEGF-C exposed to both CO2 and N2 was significantly increased compared with control group （P〈0.05）; the MMP9 expression level of CO2 group was higher than that of N2 group, P〈0.05. We concluded that carbon dioxide pneumoperitoneum may improve the adhesive and invasive ability of ovarian carcinoma cell line in vitro and CO2 can also be an independent factor to stimulate the expression of MMP9.
文摘Objective： The aim of this study was to investigate the expression of CD147 and matrix metalioprpteinsae 9 （MMP-9） in children with non-Hodgkin＇s lymphoma （NHL） and the relations between expressions of CD147 ＆ MMP-9 and the clinical indexes. Methods： Specimens excised from NHL patients were prepared. Expression of CD147 and MMP-9 were tested by SABC immunohistochemistry and its correlation to clinical results were analyzed in this report. Results： The positive rate of CD147 expression was 73% （45/62）, and that of MMP-9 expression was 81% （50/62）. There was a positive correlation between CD147 and MMP-9 expressions. CD147 expression intensity was linked to clinical myelo-infiltration, tumor size, LDH value, and clinical staging （P 〈 0.05）, rather than children age, gender, or immune typing （P 〉 0.05）; MMP-9 expression intensity was linked to myelo-infiltration, and clinical staging （P 〈 0.05）, rather than age, gender, immune typing, tumor size, or LDH value （P 〉 0.05）. Five-year survival rates were 78% （22/28） and 45% （15/34） in CD147 （-）-（＋） and （＋＋）-（＋＋＋） cases respectively, and those were 84% （21/25） and 43% （16/37） in MMP-9 （-）-（＋） and （＋＋）-（＋＋＋） cases respectively, the difference was significant. Conclusion： The elevated expression of CD147 and/or MMP-9 correlates with a poor clinical outcome in patients with NHL.
文摘Background Inflammation within vulnerable coronary plaques may cause unstable angina by promoting rupture and erosion. C-reactive protein （CRP） is the most reliable and accessible test method for clinical use for identifying coronary artery disease event. Matrix metalloproteinase 9 （MMP-9） is highly over-expressed in the vulnerable regions of a plaque. Our aim was to evaluate the plasma levels of MMP-9 and hsCRP in subjects with both unstable angina and coronary plaques, as well as in those with unstable angina without coronary plaques.
基金This project was supported by the Guangdong Natural Science Foundation, China （No. 7001601）
文摘Background Neuroprotective strategies following cardiopulmonary resuscitation （CPR） are an important focus in emergency and critical care medicine. Matrix metalloproteinases （MMPs）, especially MMP9 attracted much attention because of its function in focal brain ischemia/reperfusion injury. In the focal cerebral ischemia model in rats, SB-3CT can suppress the expression of MMP9, relieving brain edema, and there was no studies on global cerebral ischemiareperfusion injury after CPR. Methods One hundred and twenty rats were randomly assigned to sham-operated （n=40）, resuscitation treatment （n=40）, and resuscitation control （n= 40） groups. Sham-operated group rats were anesthetized only and intubated tracheally, while the resuscitation treatment and resuscitation control groups also received cardiac arrest by asphyxiation, In the resuscitation treatment group, SB-3CT was injected intraperitoneally after restoring spontaneous circulation （ROSC）, defined as restoration of supraventricular rhythm and mean arterial pressure （MAP） 〉 60 mm Hg for more than 5 minutes. The resuscitation control group also implemented ROSC without injection of SB-3CT. The rats were executed and samples were taken immediately after death, then at 3, 9, 24, and 48 hours （n=-8）. Brain tissue expression of MMP9 protein, MMP9 mRNA, water content, Evans blue content, TNF-α, IL-1, and IL-6 was measured, and the brain tissue ultramicrostructure studied with electron microscopy. Results In the resuscitation control group, brain tissue expression of MMP9 protein and mRNA, water content, Evans blue content, TNF-α, IL-1, and IL-6 were significantly elevated at 3 hours, and peaked at 24 hours after resuscitation, when compared with the sham-operated group （P 〈0.05）. 1issue ultramicrostructure also changed in the resuscitation control group. By contrast, although all these indexes were increased in the resuscitation treatment group compared with the sham-operated group （P 〈0.05）, they were lower than in the resuscitation control group （P 〈0.05）. Conclusions Expression of MMP9 protein and mRNA, water content, Evans blue content, TNF-α, IL-1, and IL-6 increased in rat brain tissue after CPR, indicating disruption of the blood-brain barrier and excess inflammatory reaction. MMP9 expression was reduced with SB-3CT, resulting in reduced brain injury.
基金Supported by Natural Science Foundation-funded Projects: Regulation Effect of Taohong-Siwu Decoction on Alpha-granule Release of Platelet in Postpartum Blood Stasis, its Active Compounds and Action Pathway (No. 81473387)Mechanism Research of Taohong-Siwu Decoction in Regulating Brain Microvascular Angiogenesis of MACO Rats Based on Platelet Microparticles as a Plaletet-Brain Microvascular Cell Messenger (No. 81503291)Natural Science Foundation Projects of Anhui Colleges and Universities: Based on the Crosstalk of NLRP3-Caspase-1 and VEGF-Notch to Explore the Effect of THSWD Regulation of "Dispelling Stasis to Promote Regeneration" by the Interaction Between Pyroptosis and Angiogenesis After Cerebral Ischemia and Reperfusion (No. KJ2019A0467)。
文摘OBJECTIVE: To explore the effects of Taohong Siwu decoction(桃红四物汤, THSWD) on the extracellular matrix of endometrium in rats following drug-induced abortion.METHODS: Thirty-six pregnant female rats were administered mifepristone and misoprostol to induce abortion, and amounts of uterine bleeding were recorded. Pathological damage and collagen accumulation were detected by hematoxylin-eosin staining and Masson’s trichrome staining in uterus, respectively. Myeloperoxidase was evaluated by immunohistochemistry.The expression levels of fibronectin, laminin, matrix metalloproteinase 9(MMP-9), and tissue inhibitor of metalloproteinase 1(TIMP-1) were quantified using western blotting.RESULTS: THSWD could promote endometrial protection in rats following drug-induced abortion.The contents of cellulose and myeloperoxidase were significantly decreased in uterine tissue of THSWD-treated groups. Moreover, THSWD significantly decreased the expression levels of fibronectin, laminin, and TIMP-1. THSWD also significantly increased MMP-9 expression and the MMP-9/TIMP-1 ratio.CONCLUSION: THSWD plays a critical role in endometrial protection by reducing extracellular matrix deposition and uterine fibrosis. These effects may have been achieved by increasing MMP-9, reducing TIMP-1, and/or altering the ratio of MMP-9/TIMP-1.
