Objective: To investigate the expression of matrix metalloproteinase-7 (MMP-7) and Fas ligand (FasL) in gastric cancer and explore their role in progression of gastric cancer. Methods: Formalin-fixed paraffin and emb...Objective: To investigate the expression of matrix metalloproteinase-7 (MMP-7) and Fas ligand (FasL) in gastric cancer and explore their role in progression of gastric cancer. Methods: Formalin-fixed paraffin and embedded tissues of primary gastric cancer and adjacent non-tumor mucosa from 113 cases were evaluated for MMP-7, FasL and Capase-3 expression by streptavidin-peroxidase (S-P) immunohistochemistry. The expression of the first two proteins in cancer cells of primary foci was compared with clinicopathological parameters of tumors. We also observed the correlation of MMP-7 and FasL expression with Caspase-3 expression in cancer cells of primary foci. Results: MMP-7 positive immunostaining was less frequently detected in adjacent epithelial cells than in cancer cells of primary foci of gastric cancer (P<0.05, 29.2% vs 69.0%), and so was FasL (P<0.05, 34.5% vs 54.0%). MMP-7 expression was associated with tumor size, Borrmann抯 classification, invasive depth, metastasis and TNM staging (P<0.05), but not with growth pattern, Lauren抯 classification, or histological classification (P>0.05). FasL expression was correlated with tumor size, invasive depth, metastasis, Lauren抯 classification, histological classification (P<0.05), while not with Borrmann抯 classification, TNM staging or growth pattern (P>0.05). Cancer cells of primary foci expressed less Caspase-3 than their adjacent epithelial cells (P<0.05, 32.7% vs 50.4%). There was an obvious correlation between FasL, MMP-7 and Caspase-3 expression in cancer cells of primary foci (P<0.05). Co-expression of MMP-7 and FasL paralleled with Caspase-3 expression in cancer cells of primary foci (P<0.05). Conclusion: MMP-7 and FasL expression was up-regulated in gastric carcinogenesis and was principally involved in progression of gastric cancer. FasL expression could reflect the differentiation of gastric cancer cells and underlie the molecular mechanisms of different pathways of gastric tumorigenesis. Co-expression of MMP-7 and FasL could have apoptosis-inducing effect on gastric cancer cells.展开更多
Objective. To investigate the role of matrix metalloproteinase-7 (MMP-7) expression in caricinogenesisand progression of gastric cancer.Methods. We studied MMP-7 expression and microvessel density (MVD) in adjacent mu...Objective. To investigate the role of matrix metalloproteinase-7 (MMP-7) expression in caricinogenesisand progression of gastric cancer.Methods. We studied MMP-7 expression and microvessel density (MVD) in adjacent mucosa and pri-mary foci of 113 cases of gastric cancer by streptavidin-biotin-immunoperoxidase method using anti-MMP-7 and anti-CD34 antibodies. MMP-7 expression and mean MVD were compared with clinicopatholog-ical features of gastric cancer, with the relationship between MMP-7 expression and MVD concerned in gastric cancer.Results. MMP-7 showed positive expression in adjacent mucosa of gastric cancer (29.20%, 33/113),less than that in gastric cancer (69.03%, 78/113). MMP-7 expression in primary foci of gastric cancerwas positively correlated with tumor size, invasive depth, metastasis and TNM staging (P＜0.05), but notwith differentiation or growth pattern of gastric cancer (P＞0.05). Positive correlation of mean MVD withtumor size, invasive depth, metastasis and TNM staging was found (P＜0.05), despite no relationshipbetween mean MVD and differentiation of gastric cancer (P＞0.05). Mean MVD was dependent on MMP-7expression in gastric cancer (P＜0.05).Conclusion. Up-regulated expression of MMP-7 played an important role in carcinogenesis and pro-gression by participating in growth, invasion, metastasis and angiogenesis of gastric cancer. MMP-7 ex-pression could be regarded as an effective and objective marker to reflect the biological behaviors of gas-tric cancer.展开更多
Objective:To explore the expression of matrix metalloproteinase-7 in serous ovarian tumors. Methods: Expression of MMP- 1 in 6 normal ovaries, 12 serous cystadenomas of ovary, 6 borderline cystadenomas of ovary, and 2...Objective:To explore the expression of matrix metalloproteinase-7 in serous ovarian tumors. Methods: Expression of MMP- 1 in 6 normal ovaries, 12 serous cystadenomas of ovary, 6 borderline cystadenomas of ovary, and 22 serous cystadenocarcinomas of ovary were studied by immunohistoc/temical SP staining. Results: No expression of MMP- 1 was detected in normal ovaries. In most serous ovarian tumors, expression of MMP-7 was detected in both the cytoplasm of tumor cells and stroma, although it was reported in other tumors that MMP- 7 was mainly expressed in the cytoplasm of tumor cells. The expression level of MMP-7 in the cytoplasm of tumor cells was statistically insignificant between serous cystadenomas of ovary, borderline cystadenomas of ovary, and serous cystadenocarcinomas of ovary. But in the stroma, the expression level of MMP-7 in borderline cystadenomas of ovary and serous cystadenocarcinomas of ovary was significantly higher than that in serous cystadenomas of ovary (P<0. 05). In borderline cystadenomas and serous cystadenocarcinomas of ovary, expression of MMP-7 could also be detected in the nuclei of some tumor cells. Conclusion: MMP-7 may play an important role in the progression of serous ovarian tumors.展开更多
BACKGROUND Increasing data indicated that long noncoding RNAs(lncRNAs)were directly or indirectly involved in the occurrence and development of tumors,including hepatocellular carcinoma(HCC).Recent studies had found t...BACKGROUND Increasing data indicated that long noncoding RNAs(lncRNAs)were directly or indirectly involved in the occurrence and development of tumors,including hepatocellular carcinoma(HCC).Recent studies had found that the expression of lncRNA HAND2-AS1 was downregulated in HCC tissues,but its role in HCC progression is unclear.Ultrasound targeted microbubble destruction mediated gene transfection is a new method to overexpress genes.AIM To study the role of ultrasound microbubbles(UTMBs)mediated HAND2-AS1 in the progression of HCC,in order to provide a new reference for the treatment of HCC.METHODS In vitro,we transfected HAND2-AS1 siRNA into HepG2 cells by UTMBs,and detected cell proliferation,apoptosis,invasion and epithelial-mesenchymal transition(EMT)by cell counting kit-8 assay,flow cytometry,Transwell invasion assay and Western blotting,respectively.In addition,we transfected miR-837-5p mimic into UTMBs treated cells and observed the changes of cell behavior.Next,the UTMBs treated HepG2 cells were transfected together with miR-837-5p mimic and tissue inhibitor of matrix metalloproteinase-2(TIMP2)overexpression vector,and we detected cell proliferation,apoptosis,invasion and EMT.In vivo,we established a mouse model of subcutaneous transplantation of HepG2 cells and observed the effect of HAND2-AS1 silencing on tumor formation ability.RESULTS We found that UTMBs carrying HAND2-AS1 restricted cell proliferation,invasion,and EMT,encouraged apoptosis,and HAND2-AS1 silencing eliminated the effect of UTMBs.Additionally,miR-873-5p targets the gene HAND2-AS1,which also targets the 3’UTR of TIMP2.And miR-873-5p mimic counteracted the impact of HAND2-AS1.Further,miR-873-5p mimic solely or in combination with pcDNA-TIMP2 had been transformed into HepG2 cells exposed to UTMBs.We discovered that TIMP2 reversed the effect of miR-873-5p mimic caused by the blocked signalling cascade for matrix metalloproteinase(MMP)2/MMP9.In vivo results showed that HAND2-AS1 silencing significantly inhibited tumor formation in mice.CONCLUSION LncRNA HAND2-AS1 promotes TIMP2 expression by targeting miR-873-5p to inhibit HepG2 cell growth and delay HCC progression.展开更多
Vascular endothelial growth factor and its mimic peptide KLTWQELYQLKYKGI(QK)are widely used as the most potent angiogenic factors for the treatment of multiple ischemic diseases.However,conventional topical drug deliv...Vascular endothelial growth factor and its mimic peptide KLTWQELYQLKYKGI(QK)are widely used as the most potent angiogenic factors for the treatment of multiple ischemic diseases.However,conventional topical drug delivery often results in a burst release of the drug,leading to transient retention(inefficacy)and undesirable diffusion(toxicity)in vivo.Therefore,a drug delivery system that responds to changes in the microenvironment of tissue regeneration and controls vascular endothelial growth factor release is crucial to improve the treatment of ischemic stroke.Matrix metalloproteinase-2(MMP-2)is gradually upregulated after cerebral ischemia.Herein,vascular endothelial growth factor mimic peptide QK was self-assembled with MMP-2-cleaved peptide PLGLAG(TIMP)and customizable peptide amphiphilic(PA)molecules to construct nanofiber hydrogel PA-TIMP-QK.PA-TIMP-QK was found to control the delivery of QK by MMP-2 upregulation after cerebral ischemia/reperfusion and had a similar biological activity with vascular endothelial growth factor in vitro.The results indicated that PA-TIMP-QK promoted neuronal survival,restored local blood circulation,reduced blood-brain barrier permeability,and restored motor function.These findings suggest that the self-assembling nanofiber hydrogel PA-TIMP-QK may provide an intelligent drug delivery system that responds to the microenvironment and promotes regeneration and repair after cerebral ischemia/reperfusion injury.展开更多
目的:探讨子痫前期(PE)患者血清和胎盘中的肿瘤坏死因子-α(TNF-α)、基质金属蛋白酶-1(MMP-1)、基质金属蛋白酶-7(MMP-7)的表达水平。方法:选取2021年11月—2023年8月扬州大学临床医学院妇产科收治的86例PE患者,分为早发型PE(n=33)和...目的:探讨子痫前期(PE)患者血清和胎盘中的肿瘤坏死因子-α(TNF-α)、基质金属蛋白酶-1(MMP-1)、基质金属蛋白酶-7(MMP-7)的表达水平。方法:选取2021年11月—2023年8月扬州大学临床医学院妇产科收治的86例PE患者,分为早发型PE(n=33)和晚发型PE(n=53),另外选取健康孕妇(n=45)作为对照。检测所有纳入患者血清及胎盘组织中的TNF-α、MMP-1和MMP-7水平。结果:早发型PE患者(34.71±1.35周vs 40.43±0.70周)及晚发型PE患者(38.43±0.60周vs 40.43±0.70周)的孕周明显小于对照组(均P<0.05);早发型PE患者血清中TNF-α(507.92±28.99 ng/L vs 478.50±41.15 ng/L)、MMP-1(1156.67±158.07μg/L vs 1037.59±163.10μg/L)和MMP-7(211.00±18.64μg/L vs 196.32±19.87μg/L)的表达较晚发型PE患者显著增加(均P<0.05),晚发型PE患者血清中TNF-α(478.50±41.15 ng/L vs 446.90±41.52 ng/L)、MMP-1(1037.59±163.10μg/L vs 840.78±174.43μg/L)和MMP-7(196.32±19.87μg/L vs 166.01±15.09μg/L)的表达较对照组显著增加(均P<0.05);免疫组化结果显示,早发型PE患者胎盘组织中TNF-α、MMP-1和MMP-7表达水平较晚发型PE及对照组明显升高(均P<0.05)。结论:早发型PE患者及晚发型PE患者的TNF-α、MMP-1和MMP-7表达明显增加,这可能在PE的发生发展中起到重要作用。展开更多
Studies have shown that Picroside Ⅱ attenuates inflammatory reactions following brain ischemia through the inhibition of the TLR-4-NF-KB signal transduction pathway, and ameliorates cerebral edema through the reducti...Studies have shown that Picroside Ⅱ attenuates inflammatory reactions following brain ischemia through the inhibition of the TLR-4-NF-KB signal transduction pathway, and ameliorates cerebral edema through the reduction of aquaporin-4 expression. Matrix metalloproteinase-9 （MMP-9）, located downstream of the TLR-4-NF-KB signal transduction pathway, can degrade the neurovascular matrix, damage the blood-brain barrier to induce cerebral edema, and directly result in neuronal apoptosis and brain injury, Therefore, the present study further observed MMP-9 expression in the brain tissues of rats with cerebral ischemia/reperfusion injury following Picroside Ⅱ treatment. Results demonstrated that Picroside Ⅱ significantly reduced MMP-9 expression in ischemic brain tissues, as well as neuronal apoptosis and brain infarct volume, suggesting Picroside Ⅱ exhibits neuroprotection by down-regulating MMP-9 expression and inhibiting cell apoptosis.展开更多
Objective: To discuss the expression and significance of angiostatin, vascular endothelial growth factor and matrix metalloproteinase-9 in the brain tissue of diabetic rats with ischemia reperfusion. Methods: A total ...Objective: To discuss the expression and significance of angiostatin, vascular endothelial growth factor and matrix metalloproteinase-9 in the brain tissue of diabetic rats with ischemia reperfusion. Methods: A total of 60 male Wistar rats were randomly divided into the normal group, sham group, diabetic cerebral infarction group and single cerebral infarction group according to the random number table, with 15 rats in each group. The high sucrose diet and intraperitoneal injection of streptozotocin were performed for the modeling of diabetic rats, while the thread-occlusion method was employed to build the model of cerebral ischemia reperfusion. The immunohistochemical staining was performed to detect the expression of angiostatin, vascular endothelial growth factor(VEGF) and matrix metalloproteinase-9(MMP-9) in the brain tissue. Results: The expression of angiostatin after the reperfusion in the brain tissue of rats in the single cerebral infarction group and diabetic cerebral infarction group was increased 6 h after the reperfusion, reached to the peak on 1 d and then decreased gradually. The expression of angiostatin in the diabetic cerebral infarction group 6 h, 1 d, 3 d and 7 d after the reperfusion was significantly higher than that in the single cerebral infarction group(P<0.05). VEGF began to be increased 1 h after the reperfusion in the single cerebral infarction group and diabetic cerebral infarction group, reached to the peak at 6 h and then decreased gradually. The expression of VEGF in the diabetic cerebral infarction group at each time point after the reperfusion was significantly lower than that in the single cerebral infarction group(P<0.05). MMP-9 began to be be increased 1 h after the reperfusion in the single cerebral infarction group and diabetic cerebral infarction group, reached to the peak on 1 d and then decreased gradually. The expression of MMP-9 in the diabetic cerebral infarction group at each time point after the reperfusion was significantly higher than that in the single cerebral infarction group(P<0.05). Conclusions: The high glucose environment in which the diabetic cerebral infarction is occurred is to induce the formation of MMP-9 at first and then activate and increase the expression of angiostatin. Afterwards, the expression of VEGF is inhibited, resulting in the poor angiogenesis after cerebral infarction, which thus makes the injury of brain tissue after cerebral infarction even worse than the non-diabetes mellitus.展开更多
Basement membrane degradation and blood-brain barrier damage appear after cerebral infarc- tion, severely impacting neuronal and brain functioning; however, the underlying pathogenetic mechanisms remain poorly underst...Basement membrane degradation and blood-brain barrier damage appear after cerebral infarc- tion, severely impacting neuronal and brain functioning; however, the underlying pathogenetic mechanisms remain poorly understood. In this study, we induced cerebral infarction in stroke- prone spontaneously hypertensive rats by intragastric administration of high-sodium water （1.3% NaC1） for 7 consecutive weeks. Immunohistochemical and immunofluorescence assays demonstrated that, compared with the non-infarcted contralateral hemisphere, stroke-prone spontaneously hypertensive rats on normal sodium intake and Wistar-Kyoto rats, matrix metalloproteinase-9 expression, the number of blood vessels with discontinuous collagen IV expression and microvessel density were significantly higher, and the number of continuous collagen IV-positive blood vessels was lower in the infarct border zones of stroke-prone sponta- neously hypertensive rats given high-sodium water. Linear correlation analysis showed matrix metalloproteinase-9 expression was positively correlated with the number of discontinuously collagen IV-labeled blood vessels and microvessel density in cerebral infarcts of stroke-prone spontaneously hypertensive rats. These results suggest that matrix metalloproteinase-9 upregula- tion is associated with increased regional angiogenesis and degradation of collagen IV, the major component of the basal lamina, in stroke-prone spontaneously hypertensive rats with high-sodi- um water-induced focal cerebral infarction.展开更多
To study the role of the reversion-inducing-cysteine-rich protein with Kazal motifs （RECK） gene and matrix metalloproteinase-2 （MMP-2） in the regulation of trophoblast invasion of early pregnancy. Immunohistochemi...To study the role of the reversion-inducing-cysteine-rich protein with Kazal motifs （RECK） gene and matrix metalloproteinase-2 （MMP-2） in the regulation of trophoblast invasion of early pregnancy. Immunohistochemistry, Western blot and gelatin zymography were used to detect the RECK protein expression localization, expression level and MMP-2 activation level in the placental tissues harvested from 52 normal pregnant women （27 in the early pregnancy, 25 in the term pregnancy）. Immunohistochemistry showed that RECK expression was found both in villous tissues of early pregnancy group and term pregnancy group and was mainly observed in cell membrane and cytoplasm of cytotrophoblasts and syneytiotrophoblasts. RECK expression increased with gestational time. RECK expression of early pregnancy group was significantly lower than that of term pregnancy group （P〈0.05）. RECK expression was significantly lower in cellular column （CC） with invasion ability. Western blot showed that the RECK protein expression in early pregnancy group was significantly lower than that in term pregnancy （P〈0.05）. The optical density values of RECK protein expression in early pregnancy group and term pregnancy group were 1.35±0.14 and 2.68±0.26, respectively, while MMP-2 activation ratio was contrary to RECK protein expression and decreased with the gestation time （P〈0.01）. The MMP-2 activation ratios of early pregnancy group and term pregnancy group were 0.46±0.05 and 0.10±0.02, respectively. The expression of the tumor inhibitory gene RECK was positively related with the invasion ability of trophoblasts, while the invasion gene MMP-2 was negatively related with the ability. The interaction between RECK and MMP-2 may play an important role in the regulation of the trophoblast invasion in early pregnancy.展开更多
Huoxue Rongluo Tablet was made of tall gastrodis tuber, dahurian angelica root, honeysuckle stem, grassleaf sweetflag rhizome, common flowering quince fruit, figwort root, red peony root and peach seed at a ratio of 3...Huoxue Rongluo Tablet was made of tall gastrodis tuber, dahurian angelica root, honeysuckle stem, grassleaf sweetflag rhizome, common flowering quince fruit, figwort root, red peony root and peach seed at a ratio of 3：2：6：2：3：3：3：3. Huoxue Rongluo Tablet is a well-established and common pre- scription for the treatment of cerebral infarction. In this study, a rat model of cerebral ischemia was established and the animals were intragastrically administered Huoxue Rongluo Tablet. This treat- ment reduced infarct volume, decreased matrix metalloproteinase-9 expression, and improved neurological function. Moreover, the effects of Huoxue Rongluo Tablet were better than those of buflomedil pyridoxal phosphate. These results indicate that Huoxue Rongluo Tablet is effective in treating cerebral infarction by regulating matrix metalloproteinase-9 protein expression.展开更多
Activity of matrix metalloproteinase-9 increases following cerebral ischemia/reperfusion, and is associated with cerebral microvascular permeability, blood-brain barrier destruction, inflammatory cell infiltration and...Activity of matrix metalloproteinase-9 increases following cerebral ischemia/reperfusion, and is associated with cerebral microvascular permeability, blood-brain barrier destruction, inflammatory cell infiltration and brain edema. Matrix metalloproteinase-9 also likely participates in thrombolysis. A rat model of middle cerebral artery infarction was established by injecting autologous blood clots into the internal carotid artery. At 3 hours following model induction, urokinase was injected into the caudal vein. Decreased neurological severity score, reduced infarct volume, and increased expression of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 were observed in the cerebral cortex 24 hours after urokinase thrombolysis. These results suggest that urokinase can suppress damage in the acute-early stage of cerebral infarction.展开更多
AIM: To compare matrix metalloproteinase (MMP)-9 and tissue inhibitor of metalloproteinase (TIMP)-1 in gastric ulcer (GU) and chronic superficial gastritis (CSG). METHODS: This study enrolled 63 patients with GU and 2...AIM: To compare matrix metalloproteinase (MMP)-9 and tissue inhibitor of metalloproteinase (TIMP)-1 in gastric ulcer (GU) and chronic superficial gastritis (CSG). METHODS: This study enrolled 63 patients with GU and 25 patients with CSG. During upper gastroduodenal endoscopy, we took samples of gastric mucosa from the antrum and ulcer site from patients with GU, and samples of antral mucosa from patients with CSG. Mucosal biopsy tissues were cultured for 24 h, and the culture supernatant was measured for levels of MMP-9 and TIMP-1. After receiving eradication therapy for Helicobacter pylori (H. pylori ) and 8 wk proton-pump inhibitor therapy for GU, follow-up endoscopy examination was performed after 6 mo and whenever severe symptoms occurred. RESULTS: Levels of MMP-9 and TIMP-1 at the ulcer site or in the antrum were significantly higher in GU than CSG patients. MMP-9 levels at the ulcer site were significantly higher than in the antrum in GU patients, and had a significantly positive correlation with TIMP-1. MMP-9 levels were significantly higher in H. pylori -positive than H. pylori -negative GU and CSG patients. Levels of MMP-9 or TIMP-1 at the ulcer site were associated with the histological severity of activity and inflammation. About 57 GU patients were followed up, and seven had GU recurrence. H. pyloriinfection and MMP-9 levels were risk factors for the recurrence of GU adjusted for age and sex by multiple logistic regression analysis. CONCLUSION: MMP-9 may perform an important function in gastric ulcer formation and recurrence.展开更多
文摘Objective: To investigate the expression of matrix metalloproteinase-7 (MMP-7) and Fas ligand (FasL) in gastric cancer and explore their role in progression of gastric cancer. Methods: Formalin-fixed paraffin and embedded tissues of primary gastric cancer and adjacent non-tumor mucosa from 113 cases were evaluated for MMP-7, FasL and Capase-3 expression by streptavidin-peroxidase (S-P) immunohistochemistry. The expression of the first two proteins in cancer cells of primary foci was compared with clinicopathological parameters of tumors. We also observed the correlation of MMP-7 and FasL expression with Caspase-3 expression in cancer cells of primary foci. Results: MMP-7 positive immunostaining was less frequently detected in adjacent epithelial cells than in cancer cells of primary foci of gastric cancer (P<0.05, 29.2% vs 69.0%), and so was FasL (P<0.05, 34.5% vs 54.0%). MMP-7 expression was associated with tumor size, Borrmann抯 classification, invasive depth, metastasis and TNM staging (P<0.05), but not with growth pattern, Lauren抯 classification, or histological classification (P>0.05). FasL expression was correlated with tumor size, invasive depth, metastasis, Lauren抯 classification, histological classification (P<0.05), while not with Borrmann抯 classification, TNM staging or growth pattern (P>0.05). Cancer cells of primary foci expressed less Caspase-3 than their adjacent epithelial cells (P<0.05, 32.7% vs 50.4%). There was an obvious correlation between FasL, MMP-7 and Caspase-3 expression in cancer cells of primary foci (P<0.05). Co-expression of MMP-7 and FasL paralleled with Caspase-3 expression in cancer cells of primary foci (P<0.05). Conclusion: MMP-7 and FasL expression was up-regulated in gastric carcinogenesis and was principally involved in progression of gastric cancer. FasL expression could reflect the differentiation of gastric cancer cells and underlie the molecular mechanisms of different pathways of gastric tumorigenesis. Co-expression of MMP-7 and FasL could have apoptosis-inducing effect on gastric cancer cells.
文摘Objective. To investigate the role of matrix metalloproteinase-7 (MMP-7) expression in caricinogenesisand progression of gastric cancer.Methods. We studied MMP-7 expression and microvessel density (MVD) in adjacent mucosa and pri-mary foci of 113 cases of gastric cancer by streptavidin-biotin-immunoperoxidase method using anti-MMP-7 and anti-CD34 antibodies. MMP-7 expression and mean MVD were compared with clinicopatholog-ical features of gastric cancer, with the relationship between MMP-7 expression and MVD concerned in gastric cancer.Results. MMP-7 showed positive expression in adjacent mucosa of gastric cancer (29.20%, 33/113),less than that in gastric cancer (69.03%, 78/113). MMP-7 expression in primary foci of gastric cancerwas positively correlated with tumor size, invasive depth, metastasis and TNM staging (P＜0.05), but notwith differentiation or growth pattern of gastric cancer (P＞0.05). Positive correlation of mean MVD withtumor size, invasive depth, metastasis and TNM staging was found (P＜0.05), despite no relationshipbetween mean MVD and differentiation of gastric cancer (P＞0.05). Mean MVD was dependent on MMP-7expression in gastric cancer (P＜0.05).Conclusion. Up-regulated expression of MMP-7 played an important role in carcinogenesis and pro-gression by participating in growth, invasion, metastasis and angiogenesis of gastric cancer. MMP-7 ex-pression could be regarded as an effective and objective marker to reflect the biological behaviors of gas-tric cancer.
基金Supported by Grant from the Natural Science Foundation of Shaanxi Province(2001K10-G4)and Scientific Research Grant of the Second Hospital of Xi'an Jiaotong University(2001YJ-22)
文摘Objective:To explore the expression of matrix metalloproteinase-7 in serous ovarian tumors. Methods: Expression of MMP- 1 in 6 normal ovaries, 12 serous cystadenomas of ovary, 6 borderline cystadenomas of ovary, and 22 serous cystadenocarcinomas of ovary were studied by immunohistoc/temical SP staining. Results: No expression of MMP- 1 was detected in normal ovaries. In most serous ovarian tumors, expression of MMP-7 was detected in both the cytoplasm of tumor cells and stroma, although it was reported in other tumors that MMP- 7 was mainly expressed in the cytoplasm of tumor cells. The expression level of MMP-7 in the cytoplasm of tumor cells was statistically insignificant between serous cystadenomas of ovary, borderline cystadenomas of ovary, and serous cystadenocarcinomas of ovary. But in the stroma, the expression level of MMP-7 in borderline cystadenomas of ovary and serous cystadenocarcinomas of ovary was significantly higher than that in serous cystadenomas of ovary (P<0. 05). In borderline cystadenomas and serous cystadenocarcinomas of ovary, expression of MMP-7 could also be detected in the nuclei of some tumor cells. Conclusion: MMP-7 may play an important role in the progression of serous ovarian tumors.
文摘BACKGROUND Increasing data indicated that long noncoding RNAs(lncRNAs)were directly or indirectly involved in the occurrence and development of tumors,including hepatocellular carcinoma(HCC).Recent studies had found that the expression of lncRNA HAND2-AS1 was downregulated in HCC tissues,but its role in HCC progression is unclear.Ultrasound targeted microbubble destruction mediated gene transfection is a new method to overexpress genes.AIM To study the role of ultrasound microbubbles(UTMBs)mediated HAND2-AS1 in the progression of HCC,in order to provide a new reference for the treatment of HCC.METHODS In vitro,we transfected HAND2-AS1 siRNA into HepG2 cells by UTMBs,and detected cell proliferation,apoptosis,invasion and epithelial-mesenchymal transition(EMT)by cell counting kit-8 assay,flow cytometry,Transwell invasion assay and Western blotting,respectively.In addition,we transfected miR-837-5p mimic into UTMBs treated cells and observed the changes of cell behavior.Next,the UTMBs treated HepG2 cells were transfected together with miR-837-5p mimic and tissue inhibitor of matrix metalloproteinase-2(TIMP2)overexpression vector,and we detected cell proliferation,apoptosis,invasion and EMT.In vivo,we established a mouse model of subcutaneous transplantation of HepG2 cells and observed the effect of HAND2-AS1 silencing on tumor formation ability.RESULTS We found that UTMBs carrying HAND2-AS1 restricted cell proliferation,invasion,and EMT,encouraged apoptosis,and HAND2-AS1 silencing eliminated the effect of UTMBs.Additionally,miR-873-5p targets the gene HAND2-AS1,which also targets the 3’UTR of TIMP2.And miR-873-5p mimic counteracted the impact of HAND2-AS1.Further,miR-873-5p mimic solely or in combination with pcDNA-TIMP2 had been transformed into HepG2 cells exposed to UTMBs.We discovered that TIMP2 reversed the effect of miR-873-5p mimic caused by the blocked signalling cascade for matrix metalloproteinase(MMP)2/MMP9.In vivo results showed that HAND2-AS1 silencing significantly inhibited tumor formation in mice.CONCLUSION LncRNA HAND2-AS1 promotes TIMP2 expression by targeting miR-873-5p to inhibit HepG2 cell growth and delay HCC progression.
基金supported by the Natural Science Foundation of Shandong Province,No.ZR2023MC168the National Natural Science Foundation of China,No.31670989the Key R&D Program of Shandong Province,No.2019GSF107037(all to CS).
文摘Vascular endothelial growth factor and its mimic peptide KLTWQELYQLKYKGI(QK)are widely used as the most potent angiogenic factors for the treatment of multiple ischemic diseases.However,conventional topical drug delivery often results in a burst release of the drug,leading to transient retention(inefficacy)and undesirable diffusion(toxicity)in vivo.Therefore,a drug delivery system that responds to changes in the microenvironment of tissue regeneration and controls vascular endothelial growth factor release is crucial to improve the treatment of ischemic stroke.Matrix metalloproteinase-2(MMP-2)is gradually upregulated after cerebral ischemia.Herein,vascular endothelial growth factor mimic peptide QK was self-assembled with MMP-2-cleaved peptide PLGLAG(TIMP)and customizable peptide amphiphilic(PA)molecules to construct nanofiber hydrogel PA-TIMP-QK.PA-TIMP-QK was found to control the delivery of QK by MMP-2 upregulation after cerebral ischemia/reperfusion and had a similar biological activity with vascular endothelial growth factor in vitro.The results indicated that PA-TIMP-QK promoted neuronal survival,restored local blood circulation,reduced blood-brain barrier permeability,and restored motor function.These findings suggest that the self-assembling nanofiber hydrogel PA-TIMP-QK may provide an intelligent drug delivery system that responds to the microenvironment and promotes regeneration and repair after cerebral ischemia/reperfusion injury.
文摘目的:探讨子痫前期(PE)患者血清和胎盘中的肿瘤坏死因子-α(TNF-α)、基质金属蛋白酶-1(MMP-1)、基质金属蛋白酶-7(MMP-7)的表达水平。方法:选取2021年11月—2023年8月扬州大学临床医学院妇产科收治的86例PE患者,分为早发型PE(n=33)和晚发型PE(n=53),另外选取健康孕妇(n=45)作为对照。检测所有纳入患者血清及胎盘组织中的TNF-α、MMP-1和MMP-7水平。结果:早发型PE患者(34.71±1.35周vs 40.43±0.70周)及晚发型PE患者(38.43±0.60周vs 40.43±0.70周)的孕周明显小于对照组(均P<0.05);早发型PE患者血清中TNF-α(507.92±28.99 ng/L vs 478.50±41.15 ng/L)、MMP-1(1156.67±158.07μg/L vs 1037.59±163.10μg/L)和MMP-7(211.00±18.64μg/L vs 196.32±19.87μg/L)的表达较晚发型PE患者显著增加(均P<0.05),晚发型PE患者血清中TNF-α(478.50±41.15 ng/L vs 446.90±41.52 ng/L)、MMP-1(1037.59±163.10μg/L vs 840.78±174.43μg/L)和MMP-7(196.32±19.87μg/L vs 166.01±15.09μg/L)的表达较对照组显著增加(均P<0.05);免疫组化结果显示,早发型PE患者胎盘组织中TNF-α、MMP-1和MMP-7表达水平较晚发型PE及对照组明显升高(均P<0.05)。结论:早发型PE患者及晚发型PE患者的TNF-α、MMP-1和MMP-7表达明显增加,这可能在PE的发生发展中起到重要作用。
基金the National Natural Science Foundation of China,No.30873391
文摘Studies have shown that Picroside Ⅱ attenuates inflammatory reactions following brain ischemia through the inhibition of the TLR-4-NF-KB signal transduction pathway, and ameliorates cerebral edema through the reduction of aquaporin-4 expression. Matrix metalloproteinase-9 （MMP-9）, located downstream of the TLR-4-NF-KB signal transduction pathway, can degrade the neurovascular matrix, damage the blood-brain barrier to induce cerebral edema, and directly result in neuronal apoptosis and brain injury, Therefore, the present study further observed MMP-9 expression in the brain tissues of rats with cerebral ischemia/reperfusion injury following Picroside Ⅱ treatment. Results demonstrated that Picroside Ⅱ significantly reduced MMP-9 expression in ischemic brain tissues, as well as neuronal apoptosis and brain infarct volume, suggesting Picroside Ⅱ exhibits neuroprotection by down-regulating MMP-9 expression and inhibiting cell apoptosis.
基金supported by Shandong Science and Technology Development Plan Project(No.Y2006C02)
文摘Objective: To discuss the expression and significance of angiostatin, vascular endothelial growth factor and matrix metalloproteinase-9 in the brain tissue of diabetic rats with ischemia reperfusion. Methods: A total of 60 male Wistar rats were randomly divided into the normal group, sham group, diabetic cerebral infarction group and single cerebral infarction group according to the random number table, with 15 rats in each group. The high sucrose diet and intraperitoneal injection of streptozotocin were performed for the modeling of diabetic rats, while the thread-occlusion method was employed to build the model of cerebral ischemia reperfusion. The immunohistochemical staining was performed to detect the expression of angiostatin, vascular endothelial growth factor(VEGF) and matrix metalloproteinase-9(MMP-9) in the brain tissue. Results: The expression of angiostatin after the reperfusion in the brain tissue of rats in the single cerebral infarction group and diabetic cerebral infarction group was increased 6 h after the reperfusion, reached to the peak on 1 d and then decreased gradually. The expression of angiostatin in the diabetic cerebral infarction group 6 h, 1 d, 3 d and 7 d after the reperfusion was significantly higher than that in the single cerebral infarction group(P<0.05). VEGF began to be increased 1 h after the reperfusion in the single cerebral infarction group and diabetic cerebral infarction group, reached to the peak at 6 h and then decreased gradually. The expression of VEGF in the diabetic cerebral infarction group at each time point after the reperfusion was significantly lower than that in the single cerebral infarction group(P<0.05). MMP-9 began to be be increased 1 h after the reperfusion in the single cerebral infarction group and diabetic cerebral infarction group, reached to the peak on 1 d and then decreased gradually. The expression of MMP-9 in the diabetic cerebral infarction group at each time point after the reperfusion was significantly higher than that in the single cerebral infarction group(P<0.05). Conclusions: The high glucose environment in which the diabetic cerebral infarction is occurred is to induce the formation of MMP-9 at first and then activate and increase the expression of angiostatin. Afterwards, the expression of VEGF is inhibited, resulting in the poor angiogenesis after cerebral infarction, which thus makes the injury of brain tissue after cerebral infarction even worse than the non-diabetes mellitus.
基金supported by the China Medical Board Project,No.82-143
文摘Basement membrane degradation and blood-brain barrier damage appear after cerebral infarc- tion, severely impacting neuronal and brain functioning; however, the underlying pathogenetic mechanisms remain poorly understood. In this study, we induced cerebral infarction in stroke- prone spontaneously hypertensive rats by intragastric administration of high-sodium water （1.3% NaC1） for 7 consecutive weeks. Immunohistochemical and immunofluorescence assays demonstrated that, compared with the non-infarcted contralateral hemisphere, stroke-prone spontaneously hypertensive rats on normal sodium intake and Wistar-Kyoto rats, matrix metalloproteinase-9 expression, the number of blood vessels with discontinuous collagen IV expression and microvessel density were significantly higher, and the number of continuous collagen IV-positive blood vessels was lower in the infarct border zones of stroke-prone sponta- neously hypertensive rats given high-sodium water. Linear correlation analysis showed matrix metalloproteinase-9 expression was positively correlated with the number of discontinuously collagen IV-labeled blood vessels and microvessel density in cerebral infarcts of stroke-prone spontaneously hypertensive rats. These results suggest that matrix metalloproteinase-9 upregula- tion is associated with increased regional angiogenesis and degradation of collagen IV, the major component of the basal lamina, in stroke-prone spontaneously hypertensive rats with high-sodi- um water-induced focal cerebral infarction.
文摘To study the role of the reversion-inducing-cysteine-rich protein with Kazal motifs （RECK） gene and matrix metalloproteinase-2 （MMP-2） in the regulation of trophoblast invasion of early pregnancy. Immunohistochemistry, Western blot and gelatin zymography were used to detect the RECK protein expression localization, expression level and MMP-2 activation level in the placental tissues harvested from 52 normal pregnant women （27 in the early pregnancy, 25 in the term pregnancy）. Immunohistochemistry showed that RECK expression was found both in villous tissues of early pregnancy group and term pregnancy group and was mainly observed in cell membrane and cytoplasm of cytotrophoblasts and syneytiotrophoblasts. RECK expression increased with gestational time. RECK expression of early pregnancy group was significantly lower than that of term pregnancy group （P〈0.05）. RECK expression was significantly lower in cellular column （CC） with invasion ability. Western blot showed that the RECK protein expression in early pregnancy group was significantly lower than that in term pregnancy （P〈0.05）. The optical density values of RECK protein expression in early pregnancy group and term pregnancy group were 1.35±0.14 and 2.68±0.26, respectively, while MMP-2 activation ratio was contrary to RECK protein expression and decreased with the gestation time （P〈0.01）. The MMP-2 activation ratios of early pregnancy group and term pregnancy group were 0.46±0.05 and 0.10±0.02, respectively. The expression of the tumor inhibitory gene RECK was positively related with the invasion ability of trophoblasts, while the invasion gene MMP-2 was negatively related with the ability. The interaction between RECK and MMP-2 may play an important role in the regulation of the trophoblast invasion in early pregnancy.
基金supported by the Scientific Research Project of Traditional Chinese Medicine of Hunan Province Chinese Medicine Research Administration Bureau in China,No.201136
文摘Huoxue Rongluo Tablet was made of tall gastrodis tuber, dahurian angelica root, honeysuckle stem, grassleaf sweetflag rhizome, common flowering quince fruit, figwort root, red peony root and peach seed at a ratio of 3：2：6：2：3：3：3：3. Huoxue Rongluo Tablet is a well-established and common pre- scription for the treatment of cerebral infarction. In this study, a rat model of cerebral ischemia was established and the animals were intragastrically administered Huoxue Rongluo Tablet. This treat- ment reduced infarct volume, decreased matrix metalloproteinase-9 expression, and improved neurological function. Moreover, the effects of Huoxue Rongluo Tablet were better than those of buflomedil pyridoxal phosphate. These results indicate that Huoxue Rongluo Tablet is effective in treating cerebral infarction by regulating matrix metalloproteinase-9 protein expression.
基金funded by the Natural Science Foundation of Shandong Province (Therapeutic effects and mechanisms of low-frequency ultrasound combined with urokinase thrombolysis in treatment of cerebral infarction in rats),No. 2009ZRB14007
文摘Activity of matrix metalloproteinase-9 increases following cerebral ischemia/reperfusion, and is associated with cerebral microvascular permeability, blood-brain barrier destruction, inflammatory cell infiltration and brain edema. Matrix metalloproteinase-9 also likely participates in thrombolysis. A rat model of middle cerebral artery infarction was established by injecting autologous blood clots into the internal carotid artery. At 3 hours following model induction, urokinase was injected into the caudal vein. Decreased neurological severity score, reduced infarct volume, and increased expression of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 were observed in the cerebral cortex 24 hours after urokinase thrombolysis. These results suggest that urokinase can suppress damage in the acute-early stage of cerebral infarction.
文摘AIM: To compare matrix metalloproteinase (MMP)-9 and tissue inhibitor of metalloproteinase (TIMP)-1 in gastric ulcer (GU) and chronic superficial gastritis (CSG). METHODS: This study enrolled 63 patients with GU and 25 patients with CSG. During upper gastroduodenal endoscopy, we took samples of gastric mucosa from the antrum and ulcer site from patients with GU, and samples of antral mucosa from patients with CSG. Mucosal biopsy tissues were cultured for 24 h, and the culture supernatant was measured for levels of MMP-9 and TIMP-1. After receiving eradication therapy for Helicobacter pylori (H. pylori ) and 8 wk proton-pump inhibitor therapy for GU, follow-up endoscopy examination was performed after 6 mo and whenever severe symptoms occurred. RESULTS: Levels of MMP-9 and TIMP-1 at the ulcer site or in the antrum were significantly higher in GU than CSG patients. MMP-9 levels at the ulcer site were significantly higher than in the antrum in GU patients, and had a significantly positive correlation with TIMP-1. MMP-9 levels were significantly higher in H. pylori -positive than H. pylori -negative GU and CSG patients. Levels of MMP-9 or TIMP-1 at the ulcer site were associated with the histological severity of activity and inflammation. About 57 GU patients were followed up, and seven had GU recurrence. H. pyloriinfection and MMP-9 levels were risk factors for the recurrence of GU adjusted for age and sex by multiple logistic regression analysis. CONCLUSION: MMP-9 may perform an important function in gastric ulcer formation and recurrence.
