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Electroacupuncture ameliorates blood-brain barrier disruption after ischemic stroke through histone acetylation regulation at the matrix metalloproteinase 9 and tissue inhibitor of metalloproteinase 2 genes

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Journal of Traditional Chinese Medicine 2024年第4期44卷 734-744页

作者： CHEN Yonglin OUYANG Ling MENG Lingling WU Bufan PENG Rou LIU Sitong HOU Dan WANG Yaling JING Xinyue LU Shengfeng FU Shuping Key Laboratory of Acupuncture and Medicine Research of Ministry of Education Nanjing University of Chinese MedicineNanjing 210023China

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 ***: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)*** MCAO model was generated by blocking the middle cerebral *** was applied to Baihui(GV20).Samples were collected 1 or 3 d after *** function scores and Evans blue extravasation were employed to evaluate the poststroke *** 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 *** RT-qPCR assay showed that EA reduced the expression of MMP-9 and promoted TIMP-2 mRNA expression,but HATi reversed these effects of *** 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 ***: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 *** findings suggested that the histone acetylation-mediated transcriptional activity of target genes may be a crucial mechanism of EA treatment in stroke.

关键词： blood-brain barrier matrix metalloproteinase 9 tissue inhibitor of metalloproteinases electroacupuncture histone acetylation

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matrix metalloproteinase 9 level as an indicator for restenosis following cervical and intracranial angioplasty and stenting

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Neural Regeneration Research 2015年第4期10卷 631-635页

作者： Jun-peng Liu Yin-zhou Wang Yong-kun Li Qiong Cheng Zheng Zheng Department of Neurology Fujian Provincial HospitalProvincial Clinical Department of Fujian Medical University

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.

关键词： nerve regeneration matrix metalloproteinase 9 cervical and intracranial angioplasty and stenting restenosis intracranial artery stenosis neural regeneration

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Integrin αvβ6 and matrix metalloproteinase 9 correlate with survival in gastric cancer

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World Journal of Gastroenterology 2016年第14期22卷 3852-3859页

作者： Pei-Long Lian Zhao Liu Guang-Yun Yang Rui Zhao Zhao-Yang Zhang Yue-Guang Chen Zhuo-Nan Zhuang Ke-Sen Xu Department of Hepatobiliary Surgery Qilu Hospital Shandong University Department of Hepatobiliary and Pancreatic Surgery Jinan Central Hospital Affiliated to Shandong University Department of Hepatobiliary Surgery Chinese People’s Liberation Army General Hospital Department of General Surgery Beijing Tsinghua Changgung Hospital Medical Center Tsinghua University

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 ***: 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 χ2 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 ***: 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

关键词： Gastric cancer Integrin α vβ 6 Prognosis matrix metalloproteinase 9 Survival

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World Journal of Diabetes 2021年第5期12卷 658-672页

作者： Nikolett Bódi Diána Mezei Payal Chakraborty Zita Szalai Bence Pál Barta János Balázs Zsolt Rázga Edit Hermesz Mária Bagyánszki Department of Physiology Anatomy and NeuroscienceFaculty of Science and InformaticsUniversity of SzegedSzeged 6726Hungary Department of Biochemistry and Molecular Biology Faculty of Science and InformaticsUniversity of SzegedSzeged 6726Hungary Department of Pathology Faculty of MedicineUniversity of SzegedSzeged 6720Hungary

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 *** To evaluate the intestinal segment-specific effects of diabetes and insulin replacement on ganglionic BM thickness, MMP9 and TIMP1 *** 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 *** 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 tenden

关键词： Type 1 diabetes Diabetic enteric neuropathy Neuronal microenvironment Basement membrane matrix metalloproteinase 9 Tissue inhibitor of metalloproteinase 1

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Effects of matrix metalloproteinase 9 inhibition on the blood brain barrier and inflammation in rats following cardiopulmonary resuscitation

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Chinese Medical Journal 2009年第19期122卷 2346-2351页

作者： HE Zhi-jie HUANG Zi-tong CHEN Xiao-tong ZOU Zi-jun Department of ICU the Second Affiliated Hospital of Sun Yat-sen University Guangzhou Guangdong 510120 China

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 r

关键词： cardiopulmonary resuscitation blood brain barrier inflammation matrix metalloproteinase 9 SB-3CT

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Comparision of high sensitivity C-reactive protein and matrix metalloproteinase 9 in patients with unstable angina between with and without significant coronary artery plaques

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Chinese Medical Journal 2011年第11期000卷 1657-1661页

作者： WANG Li-xin LU Shu-zheng ZHANG Wei-jun SONG Xian-tao CHEN Hui ZHANG Li-jie Department of Cardiology Beijing Anzhen Hospital CapitalMedical University Beijing 100029 China Institute of Biomedical Engineering Capital Medical UniversityBeijing 100069 China

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.

关键词： unstable angina high sensitivity C-reactive protein matrix metalloproteinase 9 coronary artery stenosis angiography

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Combined Detection of Serum matrix metalloproteinase 9,Acetyl Heparinase and Cathepsin L in Diagnosis of Ovarian Cancer

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Chinese Journal of Cancer Research 2012年第1期24卷 67-71页

作者： Wei Zhang Xiao-xia Hu Xing-zhi Yang Qi Wang Hong Cheng Shu-mei Wang Yan-ling Hu Zhi-jun Yang Li Li Department of Gynecologic Oncology Cancer Institute and HospitalGuangxi Medical UniversityNanning 530021China Department of Gynecology and Obstetrics the People's Hospital of Guangxi ProvinceNanning 530022China

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.

关键词： Ovarian cancer matrix metalloproteinase 9 Acetyl heparinase Cathepsin Diagnosis

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c-Met identifies a population of matrix metalloproteinase 9-producing monocytes in peritumoral stroma of hepatocellular carcinoma

c-Met identifies a population of matrix metalloproteinase 9-...

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第十四届全国肿瘤生物治疗大会

作者：赵蓝吴艳郑利民 Key Laboratory of Gene Engineering of the Ministry of Education State Key Laboratory of Biocontrol School of Life Sciences Sun Yat-sen University

Macrophages(Mφ) are prominent components of solid tumors and exhibit distinct phenotypes in different microenvironments. Previously, we found that tumors could alter the normal developmental process of Mφ to trigger transient activation of monocytes in the peritumoral stroma of human hepatocellular carcinoma(HCC). In the present study, we showed that a fraction of monocytes in the peritumoral stroma, but not in HCC cancer nests, expressed surface c-Met molecules. Monocytes exposed to tumors strongly expressed c-Met proteins with kinetics similar to their activation status, and significant correlations were found between c-Met levels and HLA-DR expression on tumor-infiltrating monocytes. NF-κB-mediated autocrine TNF-α stimulated the expression of c-Met on activated monocytes, and by interacting with its ligand HGF, c-Met regulated the retention, accumulation, and matrix metalloproteinase(MMP) 9-producing capacity of monocytes in the peritumoral stroma of HCC. The intensity of c-Met expression on tumor-infiltrating monocytes was associated with high mortality and reduced survival of patients with HCC. Therefore, the expression of c-Met on activated monocytes/Mφ may represent a novel mechanism by which a tumor actively and precisely regulates the distribution and functions of these cells to facilitate disease progression.

关键词： c-Met monocytes matrix metalloproteinase 9 hepatocellular carcinoma

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Exploring Molecular Mechanism underlying Chinese Medicine Syndrome:A Study on Correlation between Chinese Medicine Syndrome and Biomarkers for Ischemic Stroke

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Chinese Journal of Integrative Medicine 2014年第1期20卷 11-18页

作者：刘璐高颖马斌 Department of Neurology Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine

Objective：To investigate whether Chinese medicine（CM）syndrome is associated with particular molecular mechanism,we explored the correlation between CM syndrome and changes of intercellular adhesion molecule-1（ICAM-1）,matrix metalloproteinase 9（MMP-9）and heat shock protein 70（HSP70）in patients with ischemic stroke,which were reported to play an important role in the inflammatory and apoptosis ***：CM syndrome factors of 175 patients with ischemic stroke were assessed using Ischemic Stroke CM Syndrome Factor Diagnostic Scale（ISTSFDS）.The patients were grouped according to the main syndrome factor combinations at different time points based on distribution probability of syndrome factor *** levels of ICAM-1,MMP-9 and HSP70 were quantified by enzyme-linked immunosorbent ***：ICAM-1 expression was significantly higher in the internal-wind＋phlegm-dampness＋blood-stasis,phlegmdampness＋blood-stasis,internal-fire＋phlegm-dampness＋blood-stasis group than that in the blood-stasis＋qideficiency group within 72 h from stroke onset（P〈0.05）;HSP70 expression was significantly lower in the phlegm-dampness＋blood-stasis,internal-fire＋phlegm-dampness＋blood-stasis,blood-stasis group than that in the phlegm-dampness＋blood-stasis＋qi-deficiency group on the 7th day from stroke onset（P〈0.05）.Conclusions：Phlegm-dampness and blood-stasis exist through the whole process of ischemic *** increased level of ICAM-1 and a reduced level of HSP70 reflect the pathological state of phlegm-stasis mutual *** results suggest that inflammation and apoptosis induced by cerebral vascular injury in the pathological processes of ischemic stroke are more prominent in the excess syndrome state like phlegm-dampness and blood-stasis.

关键词： ischemic stroke Chinese medicine syndrome intercellular adhesion molecule-1 matrix metalloproteinase 9 heat shock protein 70

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Role of lymphotoxin alpha as a new molecular biomarker in revolutionizing tear diagnostic testing for dry eye disease

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International Journal of Ophthalmology(English edition) 2023年第11期16卷 1883-1889页

作者： Chao-Ran Li Tianjin Medical University Eye Hospital Tianjin 310011China

Dry eye disease(DED),primarily classified as multifactorial ocular surface disorder,afflicts tens of millions of individuals worldwide,adversely impacting their quality of *** research has been conducted on tear film analysis over the past decades,offering a range of tests to evaluate its volume,health,and ***,early diagnosis and effective treatment for DED continue to pose significant challenges in clinical ***,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 *** information serves as a valuable resource not only for clinical diagnosis but also for further research into DED.

关键词： dry eye disease tear film biomarker matrix metalloproteinase 9 lymphotoxin alpha

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