Neuroprotective effect of exogenous hydrogen sulfide and the expression of matrix metalloproteinases-9 and Caspase-1 in mice model of Parkinson’s disease / 解剖学报

[Abstract] Objective To investigate the protective effect of exogenous hydrogen sulfide (H

Anti-MMP-2 and MMP-9 activity of Salsola komarovii Iljin extract and its solvent fractions

Objective: To investigate matrix metalloproteinases (MMP)-2 and MMP-9 inhibitory effect of Salsola komarovii Iljin, an edible halophyte with health beneficial effects. Methods: Salsola komarovii crude extracts (SKI), and solvent (n-hexane, 85% aq. MeOH, n-BuOH, and H

Anti-MMP-2 and MMP-9 activity of Salsola komarovii Iljin extract and its solvent fractions

Objective: To investigate matrix metalloproteinases (MMP)-2 and MMP-9 inhibitory effect of Salsola komarovii Iljin, an edible halophyte with health beneficial effects. Methods: Salsola komarovii crude extracts (SKI), and solvent (n-hexane, 85％ aq. MeOH, n-BuOH, and H2O) fractionated extracts of SKI were prepared. Gelatin zymography was carried out to observe MMP enzymatic activity. The release of the MMP enzymes was measured by enzyme-linked immunosorbent assay. Expression of MMPs in mRNA and protein level were investigated by polymerase chain reaction analysis and immunoblotting, respectively. Results: SKI and SKI fractions inhibited active MMP-2 and MMP-9 amount in the treated cell culture medium. Also, SKI suppressed the release of MMP-2 and MMP-9 from stimulated HT1080 human fibrosarcoma cells. Furthermore, SKI suppressed the mRNA and protein expression of MMP-2 and MMP-9. SKI fractions showed parallel effects except for H2O fraction which did not yield any significant MMP inhibitory effect. Among fractions, 85％ aq. MeOH was the most active fraction to inhibit both the enzymatic effect and expression of MMP-2 and MMP-9. Conclusions: SKI may contain potential MMP release inhibitory compounds. Salsola komarovii is a promising source of compounds against MMP and could be utilized in the development of antitumor agents.

Clinical evaluation of Kudiezi injection in acute cerebral infarction and its effects on serum VEGF, S-100βand MMP-9 levels / 中国生化药物杂志

Objective To investigate clinical evaluation of Kudiezi injection in treatment of acute cerebral infarction and its effects on serum vascular endothelial growth factor(VEGF), S-100β, matrix metalloproteinases(MMP)-9 levels.Methods 98 patients of acute cerebral infarction who received therapy from October 2014 to October 2016 in our hospital were selected.Those patients were randomly divided into the observation group and the control group with 48 cases in each group.The control group was treated with routine treatment, while the observation group was treated with Kudiezi injection.After treatment of 14 days, the clinical curative effect, serum VEGF, S-100β, MMP-9, National institutes of health stroke scale (NIHSS) and Barthel index were compared.Results After treatment, the total effective rate in the observation group 87.75%(43/49) was significantly higher than that of the control group 65.31%( 32/49 ) , the difference was statistically significant ( P<0.05 ) , the level of VEGF in the observation group was significantly higher than that of the control group, and the S-100βand MMP-9 were significantly lower than that of the control group, the difference was statistically significant (P<0.05), the NIHSS score in the observation group was significantly lower than that of the control group, the difference was statistically significant (P<0.05), the Barthel index in the observation group was significantly higher than that of the control group, the difference was statistically significant (P<0.05).Conclusion Kudiezi injection is well for acute cerebral infarction, which can effectively improve the serum levels of VEGF, S-100β, MMP-9, and can improve the therapeutic effect, promote the recovery of neurological function and improve the quality of life.

Expression of serum vascular endothelial growth factor and matrix metalloproteinases 9 in patients with esophageal carcinoma and their clinical significances / 肿瘤研究与临床

Objective To investigate the relationship between the expressions of serum vascular endothelial growth factor (VEGF), matrix metalloproteinases 9 (MMP-9) before and after chemoradiotherapy and biological behaviors for patients with esophageal cancer. Methods The data of 65 cases with esophageal cancer were analyzed respectively, including 44 cases of primary esophageal cancer and 21 cases of postoperative esophageal cancer. Serum VEGF and MMP-9 before and after chemoradiotherapy were measured, and their relationship with clinicopathological features of esophageal cancer patients was also investigated. Results Serum VEGF level in primary patients [613.50 ng/ml (387.00 - 1127.00 ng/ml)] was significant higher than that in postoperative patients [78.00 ng/ml (40.00 - 196.50 ng/ml)] (Z= -3.493, P= 0.000). There was no difference in serum MMP-9 level with or without surgery, and serum MMP-9 level in primary patients [686.00 ng/ml (434.00 - 1211.25 ng/ml)] has no difference in postoperative patients [637.00 ng/ml (362.00-906.50 ng/ml)] (Z=-0.743, P=0.457). There was no significant correlation in serum VEGF, MMP-9 level with gender, age, tumor pathological type and tumor location in postoperative and primary patients (all P>0.05). There was no significant difference in serum VEGF, MMP-9 level before or after chemoradiotherapy in postoperative patients (P=0.339, P=0.689), but there was a difference in primary patients (P= 0.000, P= 0.001). The changes of serum VEGF, MMP-9 levels were synergistic (r= 0.451, P<0.001). Conclusion The dynamic monitoring and comparison of serum VEGF, MMP-9 levels can predict the efficacy of esophageal cancer and guide the individualized therapy.

Effects of celecoxib and amniotic membrane suspension on neovascularization area and expression of MMP-2,mmp-9 in corneal thermal-burned rabbit / 眼科新进展

Objective To compare the effects of celecoxib and amniotic membrane suspension (AMS) on corneal neovascularization (CNV) area and expression of matrix metalloproteinase-2 (MMP-2) and matrix metalloprotein-ase-9 (MMP-9) in the growth of corneal neovascularization after thermal burn in rabbits,and provide a theoretical basis of celecoxib for the clinical treatment of corneal neovascularization.Methods Left corneas of 36 rabbits were burned by the home-made burning-device,and randomly divided to three groups:negative control group (n =12),AMS group (n =12) and celecoxib group (n =12),were respectively sub-conjunctival injected by 90 g · L-1 saline (0.1 mL),AMS (0.1 mL) and 8 mg · mL-1 celecoxib solution (0.1 mL).The histological morphology,growth condition and area of CNV were compared under slit lamp microscope at 4 days,7 days and 14 days after thermal-burned.At 7 days after thermal-burned,four appropriate corneas were randomly taken to detect the expression of MMP-2 and MMP-9 by immunohistochemistry,and the results were analyzed by computer image analysis system.Results At 4 days,7 days,14 days after thermal-burned,the areas of neovascularization were (11.32 ± 1.11)mm2,(38.49 ± 4.64) mm2,(43.30 ± 4.39) mm2 in negative control group,(9.69 ± 1.30) mm2,(31.15 ± 4.85)mm2,(37.19 ± 5.27) mm2 in AMS group,(8.47 ± 1.20)mm2,(30.31 ± 4.93) mm2,(36.69 ± 3.54) mm2 in celecoxib group,respectively.At different time points,neovascularization area in AMS group or celecoxib group was significantly lower than negative control group (all P ＜ 0.05).There was no difference between AMS and celecoxib group (all P ＞ 0.05).At 7 days after thermal-burned,the expression of MMP-2 and MMP-9 was not different between AMS group and celecoxib group (all P ＞ 0.05),and significantly lower than negative control group (all P ＜ 0.05).Conclusion Celecoxib and amniotic membrane suspension can all effectively inhibit CNV after thermal-burned,which may be related to the down-regulated expression of MMP-2,MMP-9 in thermal-burned corneas.

The expression and significance of matrix metalloproteinases-9 and tissue inhibitors of matrix metalloproteinase-1 in serum of infant with severe pneumonia / 中国小儿急救医学

Objective To explore the expression and significance of matrix metalloproteinases-9(MMP-9) and tissue inhibitors of matrix metalloproteinase-1(TIMP-1) in serum at acute phase of severe pneumonia in infants.Methods A total of 45 infants of pneumonia were selected and divided into 20 cases of severe pneumonia group and 25 cases of mild pneumonia group according to the severity of the disease,and all 45 infants were also divided into virus group of 24 cases and non-virus group of 21 cases on the basis of etiology.Additionally,20 cases of healthy children who accepted the physical examination at the same time were selected as the control group.Serum levels of MMP-9 and TIMP-1 were detected by using ELISA.Tidal breathing lung function was measured in all selected infants.Results Compared with the control group,the serum levels of MMP-9,TIMP-1 and MMP-9/TIMP-1 ratio of the infants with acute pneumonia were significantly higher,the severe pneumonia group were higher than the mild pneumonia group,and the virus group were higher than the non-virus group(P＜0.05).The ratio of the time to reach peak tidal expiratory flow to total expiratory time (TPTEF/TE) and the volume to reach peak tidal expiratory flow to total expiratory volume(VPTEF/VE) of pneumonia group in recovery period were significantly lower than those in the control group,severe pneumonia group were lower than those in the mild pneumonia group,and the virus group were lower than those in the non-virus group (all P＜0.05).There were no statistically significant about VT/kg among three groups.The serum MMP-9 levels and the MMP-9/TIMP-1 ratio were negatively correlated with TPTEF/TE and VPTEF/VE (r1=-0.459,-0.376; r2=-0.413,-0.327; all P＜0.05).Conclusion The serum levels of MMP-9 and the MMP-9/TIMP-1 ratio in the acute phase of infantile pneumonia are correlated with pneumonia severity and pulmonary function injury in recovery period,and the performance is particularly prominent in the viral pneumonia,and can be used as a prognosis monitoring indicator.

Effects of propofol on rat brain function and tPA/MMP9 expression / 中国病理生理杂志

AIM: To investigate the effects of propofol on the expression of tissue-type plasminogen activator (tPA) and matrix metalloproteinase 9 (MMP9) in the hippocampus and the cognitive function in neonatal rats.METHODS: The 7-day-old rats were randomly divided into 3 groups: the rats in control (CON) group were intraperitoneally injected with normal saline for 7 d;the rats in single dose of propofol anesthesia (SP) group were intraperitoneally injected with normal saline for 6 d and with propofol on the 7th day;the rats in repeated dose of propofol anesthesia (RP) group were intraperitoneally injected with propofol for 7 d.Blood glucose and blood gas analysis were tested in 6 rats of each group.The rats were randomly selected from each group to isolate the hippocampal tissues at 2 h, 24 h, 48 h, 72 h and 30 d after the last injection.The spatial learning and memory functions of the other rats aged 25 d were determined by Morris water maze.The morphological changes of the hippocampus were observed by HE staining and Nissl's staining.The expression of tPA and MMP9 at mRNA and protein levels was determined by RT-PCR and Western blot.RESULTS: Compared with group CON, the protein expression of tPA and MMP9 in RP group was significantly decreased at each time point, while no significant decrease was observed in SP group except at the time point of 24 h.Compared with CON group, the mRNA expression of tPA and MMP9 was down-regulated obviously in RP group, which was not significantly down-regulated in SP group.From the 3rd training day of Morris water maze beginning, the escape latency was prolonged, and the space exploration time and the number of crossing the original platform location were reduced in RP group compared with CON group and SP group, while no significant difference was observed between CON group and SP group.Compared with CON group, the number of nerve cells reduced and nerve cells arranged in disorder in the hippocampus in RP group.Moreover, the number of Nissl body decreased significantly and finally developed into neuronal degeneration and necrosis in RP group, and no significant difference between SP group and CON group was observed.CONCLUSION: Repeated dose of propofol anesthesia leads to long-term cognitive dysfunction in neonatal rats, which may be related to the down-regulation of tPA and MMP9 expression and destruction of normal morphology and function of neurons in hippocampus, whereas single dose of propofol anesthesia has no such effects.

Effect of apolipoprotein E on matrix metalloproteinases-9 expression and its mechanism in astrocytes / 中华神经医学杂志

Objective To explore the effect of apolipoprotein E (ApoE) on matrix metalloproteinases-9 (MMP-9) expression and its mechanism in astrocytes.Methods (1) Astrocytes in ApoE gene knock out (ApoE-/-) and wild type (WT) C57BL/6J suckling mice were cultured in vitro;glial fibrillary acidic protein antibodies were employed to identify the astrocytes;MMP-9.antibodies were employed to detect the MMP-9 expression in the astrocytes.(2) Astrocytes from the ApoE-/-and wild type WT C57BL/6J suckling mice were divided into activation group,antibody groups and control group randomly;cells in the control group did not give any treatment;cells in the activation group were given whooping cough toxin and thermal inactivation-mycobacterium tuberculosis H37Ra;cells in the antibody groups were given anti-interleukin-6 (IL-6),interferon gamma (IFN--γ),tumor necrosis factor-α (TNF-α) and IL-12,respectively,to inhibit their inflammatory factors.ELISA was performed to detect the concentrations of MMP-9 and tissue inhibitor of metalloproteinase-1 (TIMP-1),and the inflammatory factors concentrations ofTNF-,IL-12,IL-6,and IFN-γ.Results These two kinds of rat astrocytes could both qualitatively express MMP-9;as compared with the control group,the activation group had significantly higher MMP-9 concentration (P＜0.05);the activation group had significantly higher MMP-9 concentration as compared with the antibody groups (P＜0.05);activation group from ApoE-/-C57BL/6J suckling mice had significantly higher MMP-9 concentration than that from wild type C57BL/6J suckling mice (P＜0.05).The concentration of TIMP-1 was not significantly different among various groups (P＞0.05).The concentrations of inflammatory factors in the activation groups from two kinds of mice were significantly higher than those in the control group (P＜0.05);the concentrations of IL-6,IFN-γ TNF-α and IL-12 in each antibody group were significantly lower than those in the activated group (P＜0.05);the concentrations of inflammatory factors in ApoE-/-rats were significantly higher than those in WT rats (P＜0.05).Conclusion ApoE can regulate the MMP-9 expression by regulating the secretion of proinflammatory cytokines,which can affect the integrity of blood brain barrier.

Significance of detection of serum Omentin-1 and MMP 9 level in patients with ischemic stroke complicating multiple sclerosis / 国际检验医学杂志

Objective To investigate the significance of serum Omentin-1 and matrix metalloproteinases-9 (MMP 9) level detec-tion in the patients with ischemic stroke complicating multiple sclerosis (MS) .Methods A total of 169 patients with ischemic stroke in our Hospitals from September 2013 to September 2016 were selected as the diseases group and divided into the combined group (n=57 cases) and single disease group (n=112) according to whether complicating DS .Contemporaneous 30 health persons in the physical examination center were chosen as the health group .The enzyme-linked immunosorbent assay (ELISA) was used to detect serum Omentin-1 and MMP-9 levels in all subjects .Then the serum Omentin-1 and MMP-9 levels and neural function were statisti-cally analyzed .Results Serum MMP-9 level and EDSS score in the disease group were significantly higher than those in the healthy group ,the serum Omentin-1 levels of the former was significantly lower than that of the latter ;serum MMP-9 level and expaned disability status Scale(EDSS) score in the combined group were significantly higher than those in the single disease group ,the ser-um Omentin-1 levels of the former was significantly lower than that of the latter ,the difference was statistically significant (P<0 .05);The Pearson correlation analysis results showed that the serum Omentin-1 level was negatively correlated with the EDSS score (r= -0 .724 ,P<0 .05) ,the serum MMP-9 level was positively correlated with the EDSS score (r=0 .763 ,P<0 .05);the Logistic regression analysis results showed that low serum Omentin-1 level ,high MMP-9 level of and high EDSS score were the in-dependent risk factors for ischemic stroke complicating MS (P<0 .05);the ROC curve analysis results showed that serum Omentin-1 level of 180 ng/mL serving as the cutoff value and serum M M P-9 level of 260 ng/mL as the cutoff value ,the sensitivity ,specific , accuracy of their combination for predicting ischemic stroke complicating MS were 94 .74% ,96 .43% and 95 .86% respectively . Conclusion Serum Omentin-1 and MMP-9 levels are related with the occurrence and development of ischemic stroke complicating MS ,are the independent risk factors for the latter occurrence ,moreover can effectively assess the patient′s neurologic disability situ-ation ,their joint detection can effectively assist doctors to assess the patient′s condition change ,and can effectively predict the oc-currence of ischemic stroke complicating MS ,which is worth further clinical promotion .

Effect of Tanreqing Injection on Serum Levels of TGF-β and MMP-9 of Patients with COPD / 现代生物医学进展

Objective:To analyze the effect of tanreqing injection on the serum levels of transforming growth factor-β (TGF-β) and matrix metalloproteinases-9 (MMP-9) of patients with chronic obstructive pulmonary disease (COPD).Methods:102 patients with COPD were divided into the control group and the observation group according to random number table method,52 cases in each group.The control group was treated with routine therapy,and the observation group was treated with Tanreqing injection based on the control group.The serum TGF-β,MMP-9 levels,forced vital capacity (FVC),1 s forced expiratory volume (FEV1),partial pressure of carbon dioxide (PaCO2),oxygen partial pressure (PaO2),CD4+,CD86,CD4+/CD8+,syndrome integral,clinical efficacy and incidence of side effects were observed and compared between the two groups.Results:After treatment,the serum TGF-β,MMP-9 levels,PaCO2 and syndrome integral of observation group were significantly lower than those of the control group,the PaO2,CD4+,FVC,FEV1,CD4+/CD8+ and the clinical efficacy of observation group were obviously higher than those of the control group (P＜0.05).There was no significant difference in the incidence of side effects between the two groups (P＞0.05).Conclusion:Tanreqing injection could effectively reduce the serum levels of TGF-β and MMP-9,and improve the arterial blood gas,lung function and immune function in treatment of patients with COPD.

An association study between matrix metalloproteinase-9 gene polymorphisms and ischemic stroke / 中国神经精神疾病杂志

Objective Objective TO investigate the potential association between matrix metalloproteinase-9 (MMP-9) gene polymorphisms and risk of ischemic stroke in Western Guangdong population.Methods This hospitalbased case-control study recruited 251 patients with ischemic stroke and 96 controls.Using Multiplex SNaPshot method was used to detect the genotype of MMP-9 gene rs3787268、rs3918241 and rs3918242 polymorphisms.The association between MMP-9 gene polymorphisms and risk of ischemic stroke was analyzed.Results ① There were significant differences in the genotype distribution of rs3787268 between ischemic stroke group and the controls (P=0.042).In the recessive model,the individual risk of A/A genotype was higher (OR=2.21,P=0.046) than that of the G/G+G/A genotype.② Compared with the controls,the genotype and allele distribution of rs3918242 in the ischemic stroke group were significantly different (P=0.007,P=0.038).In the dominant model,the risk of individuals carrying the T genotype was significantly elevated (OR=2.14,P=0.009) compared with individuals with the C/C genotype.③ The genotype distribution of rs3787268 polymorphisms in the LAA but not in no-LAA subgroup was significantly different from that in the controls (P =0.039).The genotype distribution and allele frequency of rs3918242 polymorphisms in the LAA subgroup were significantly different from that of the control group (P=0.009,P=0.047).There was no significant difference in the genotype distribution and allele frequency between no-LAA subtype and the control group.Conclusions The MMP-9 gene rs3918242 and rs3787268 polymorphisms may be the risk factors of ischemic stroke in Han population in the western part of Guangdong province,China.The MMP-9 gene rs3918242 and rs3787268 polymorphisms may be the risk factors of large-artery atherosclerotic stroke.

Effect of Berberine on Neurological Function,Serum Oxidized Low Density Lipoprotein and Matrix Metalloproteinases-9 in Patients with Acute Cerebral Infarction / 医药导报

Objective To observe the effects of berberine on neuralogical function,serum oxidized low density lipoprotein(ox-LDL),and matrix metalloproteinases-9(MMP-9) in patients with acute cerebral infarction.Methods Ninety-two patients with acute cerebral infarction were randomly divided into treatment group and control group (n=46).Control group received routine treatment,while treatment group was given 0.3 g of berberine three times a day besides routine treatment for 14 days.In both groups,decubitus venous blood was harvested before,7 and 14 days after treatment.Serum ox-LDL and MMP-9 were determined with enzyme-linked immunosorbent assay (ELISA).Before and 7 and 14 days after treatment,the neural function defect was graded by the US National Institutes of health stroke scale (NIHSS) and the modified Rankin scale (mRS).Results The neurological function was improved significantly in 7 and 14 days after the treatment for both two groups according to NIHSS and mRS,and the difference between treatment group and control group was statistically significant (P<0.05).After treatment,ox-LDL and MMP-9 declined significantly in both groups,and were lower in treatment group than in control group (all P<0.05).Conclusion Berberine significantly reduces ox-LDL and MMP-9 levels in patients with acute cerebral infarction and improves the degree of neurological function deficit.

Pyrrolidine dithiocarbamate alleviated rat cervical intervertebral disc degeneration via reducing tumor necrosis factor α and matrixmetalloproteinase 9 expression and its underlying mechanism / 中国药理学通报

Aim To observe the effect of pyrimidine dithiocarbamate (PDTC) on the variance of disc morphology and the expressions of TNF-α, MMP-9 in the cervical disc in cervical dynamic equilibrium rat models, and to investigate the roles of PDTC in the process of intervertebral disc degeneration and the mechanism involved.Methods Fifty-four SD rats were divided into three groups randomly, then the dynamic equilibrium rat model was established by cutting the nuchal superficial and deep muscle of the rats.The dynamic equilibrium rats with PDTC solution intraperitoneal injection after operations were defined as PDTC group (group A), the models with saline intraperitoneal injection after operations as saline group (group B), the rats of fake operation with saline intraperitoneal injection as blank group (group C), and the animals were sacrificed in batches 10 weeks, 12 weeks, 16 weeks respectively after operation.The C5, C6 vertebrae and C5/6 discs were harvested, and the disc morphology was observed.TNF-α, MMP-9 mRNA expressions were detected by q-PCR and protein expression was observed by Western blot.Results Compared with the saline group, the morphology of disc in PDTC group was destructed slightly and fiber ring arranged orderly.TNF-α, MMP-9 gene and protein expressions had no obvious changes (P>0.05) in blank group (group C) at each time point.The expressions of IL-6, MMP-9 mRNA increased with time in group B, but the amount increased fast firstly, and slow lately, reaching peak in 12 weeks.The expression of TNF-α, MMP-9 protein became steady in group B from 10 weeks compared with other time points(P>0.05).TNF-α, MMP-9 genes and proteins expression decreased obviously in PDTC group (group A) compared with saline group (group B) (P<0.01) at each time point, but higher than blank group C(P<0.01) at each time point.Conclusions TNF-α and MMP-9 are important inflammatory factors involved in rat cervical disc degeneration, PDTC relieves the degeneration of rat cervical disc by reducing the expression of TNF-α and MMP-9 via disturbing the NF-κB signal pathway probably, and PDTC may become potential medicine for disc degeneration.

Study on the carvacrol induced apoptosis in human non-small cell lung cancer cell line H1299 / 天津医药

Objective To study whether carvacrol can cause apoptosis in non-small cell lung cancer (NSCLC) cell line NCI-H1299, and explore its possible molecular mechanism. Methods NCI-H1299 cells were treated with different concentrations of carvacrol (20, 40, 60 and 80μmol/L) for 24 or 48 h. The viability of cells was evaluated by MTT assay, apoptosis was analyzed by flow cytometry (FCM) and the effect of carvacrol on metastasis of NCI-H 1299 was analyzed by Transwell assay. The expression level of caspase-9, MMP-9 and TIMP-1 were detected by quantitative realtime-PCR and Western blot assay. Results After treatment with carvacrol, the viability of NCI-H1299 cells was suppressed dramatically (P0.05). After being incubated with carvacrol for 24 h, FCM analysis indicated that carvacrol effectively induced apoptosis in NCI-H1299 cells (P0.05). The ability of invasion was decreased (40.67±3.63 vs. 76.00±5.78). Carvacrol inhibited the protein and mRNA expression levels of caspase-9, but increased the expression of MMP-9 and TIMP-1 (P<0.05). Conclusion Carvacrol can induce apoptosis of NCI-H1299 cells and inhibit their invasion, which may be associated with up-regulation of caspase-9 expression and down-regulation of MMP-9 expression.

Expression of pituitary tumor-transforming gene 1 during the development of androgen-independent prostate cancer / 中华男科学杂志

<p><b>Objective</b>To explore the expression of pituitary tumor transforming gene 1 (PTTG1) during the transformation of prostate cancer from androgen-dependent (ADPC) to androgen-independent (AIPC).</p><p><b>METHODS</b>We established an AIPC cell model LNCaP-AI by culturing the androgen-dependent LNCaP cell line in the hormone-deprived medium for over 3 months. The cell model was verified and the PTTG1 expression in the LNCaP cells was detected by Western blot and RT-PCR during hormone deprivation.</p><p><b>RESULTS</b>The AIPC cell model LNCaP-AI was successfully established. The PTTG1 expression was gradually increased in the LNCaP cells with the prolonged time of hormone deprivation and the expressions of matrix metalloproteinases MMP-2 and -9 were elevated at the same time.</p><p><b>CONCLUSIONS</b>The expression of PTTG1 is increased gradually in AIPC, which may be a target of gene therapy for advanced prostate cancer.</p>

Expressions and significances of Kiss-1 and matrix metalloproteinases-9 proteins in the colorectal cancer tissues of patients with synchronous colorectal liver metastasis / 中华消化外科杂志

Objective To investigate the expressions and correlations of Kiss-1 and matrix metalloproteinases-9 (MMP9) proteins in the colorectal cancer (CRC) tissues of patients with synchronous colorectal liver metastasis (SCRLM),and the association with the clinicopathologic factors and prognosis of patients.Methods The retrospective case-control study was adopted.The clinicopathological data of 96 patients with SCRLM and 69 patients with CRC and no metastasis who were admitted to the Eastern Hepatobiliary Surgery Hospital of the Second Military Medical University from January 2000 to May 2013 were collected.The 96 CRC tissues and 50 adjacent normal tissues (distance from resection margin ≥ 5 cm) were collected from 96 patients with SCRLM,and 69 CRC tissues were collected from 69 patients with CRC and no metastasis.Expressions of Kiss-1 and MMP9 protein were detected by immunohistochemistry (IHC).The follow-up of outpatient examination and telephone interview was performed to detect survival of patients till August 2014.Comparison of count data and correlation between expressions of Kiss-1 or MMP9 protein and clinicopathological factors were analyzed by the chi-square test and Fisher exact probability.Survival curve was drawn using the Kaplan-Meier method,and survival analysis was done using the Log-rank test.Correlation analysis was done by the Pearson correlation.Results Expression of Kiss-1 protein was located in the cytoplasm of tissue cells.The positive expression rates of Kiss-1 protein in CRC tissues of patients with SCRLM and with CRC and no metastasis and in adjacent normal tissues were 24.0％ (23/96),43.5％ (30/69) and 52.0％ (26/50),respectively,with a significant difference among the 3 tissues (x2 =14.307,P ＜ 0.05) and no significant difference between CRC tissues of patients with CRC and no metastasis and patients with SCRLM (x2 =0.845,P ＞ 0.05).The positive expression rate of Kiss-1 protein in CRC tissues of patients with SCRLM was significantly different from that in CRC tissues of patients with CRC and no metastasis and in adjacent normal tissues (x2 =0.702,11.594,P ＜ 0.05).Expression of MMP9 protein was located in the cytoplasm of tissue cells.The positive expression rates of MMP9 protein in CRC tissues of patients with SCRLM and with CRC and no metastasis and in adjacent normal tissues were 67.7 ％ (65/96),62.3 ％ (43/69) and 36.0％ (18/50),respectively,with a significant difference among the 3 tissues (x2=14.203,P ＜0.05) and no significant difference between CRC tissues of patients with CRC and no metastasis and patients with SCRLM (x2=8.038,P ＞ 0.05).The positive expression rate of MMP9 protein in CRC tissues of patients with SCRLM was significantly different from that in CRC tissues of patients with CRC and no metastasis and in adjacent normal tissues (x2 =13.475,13.475,P ＜ 0.05).The positive expression rates of Kiss-1 protein in CRC tissues of patients with SCRLM were 66.7％,21.9％ and 17.6％ in the high-,mederate-and low-differentiated tumor,50.0％,28.6％ and 17.5％ in the muscular layer of tumor invasion,outside of serosa and serosal layer,44.0％ and 16.9％ in patients with and without lymph node metastasis,respectively,showing significant differences among the tumor differentiation degree,depth of tumor invasion and lymph node metastasis (x2=6.546,6.172,7.453,P ＜0.05).The positive expression rates of MMP9 protein in CRC tissues of patients with SCRLM were 25.0％,66.7％ and 76.2％ in the muscular layer of tumor invasion,outside of serosa and serosal layer,44.0％ and 76.1％ in patients with and without lymph node metastasis,respectively,showing significant differences between the depth of tumor invasion and lymph node metastasis (x2 =12.094,8.690,P ＜ 0.05).All the 96 patients with SCRLM were followed up for a median time of 68 months (range,12-176 months).The median overall survival time,median tumor-free survival time,5-year cumulative survival rate and 5-year tumor-free survival rate were 31 months,26 months,69.6％ and 26.1％ in patients with SCRLM and positive expression of Kiss-1 protein and 26 months,19 months,24.7％ and 12.3％ in patients with SCRLM and negative expression of Kiss-1 protein,respectively,showing significant differences between the overall survival and tumor-free survival (x2=16.578,14.436,P ＜ 0.05).The median overall survival time,median tumor-free survival time,5-year cumulative survival rate and 5-year tumor-free survival rate were 31 months,19 months,24.6％ and 12.3％ in patients with SCRLM and positive expression of MMP9 protein and 28 months,16 months,58.1％ and 22.6％ in patients with SCRLM and negative expression of MMP9 protein,respectively,showing significant differences between the overall survival and tumor-free survival (x2=14.073,8.532,P ＜0.05).Of 96 patients with SCRLM,there were 23 patients with positive expression of Kiss-1 protein (10 with positive expression of MMP9 protein and 13 with negative expression of MMP9 protein) and 73 with negative expression of Kiss-1 protein (55 with positive expression of MMP9 protein and 18 with negative expression of MMP9 protein),with a negative correlation between expressions of Kiss-1 protein and MMP9 protein (r =-0.291,P ＜ 0.05).Conclusions The reduced expression of Kiss-1 protein and elevated expression of MMP9 protein are closely associated with invasion and metastasis of CRC and prognosis of patients.A combination detection of Kiss-1 and MMP9 proteins is expected to become a marker for predicting the prognosis of patients with SCRLM based on the negative correlation between them.

Alteration of Blood-spinal Cord Barrier and Matrix Metalloproteinases-9 in Mice after Spinal Cord Injury / 中国康复理论与实践

Objective To investigate the influence of matrix metalloproteinases-9 (MMP-9) on permeability of blood-spinal cord barrier (BSCB) after spinal cord injury (SCI). Methods 68 male C57BL/6 mice were randomly divided into sham group, 2 days group (S2), 7 days group (S7) and 14 days group (S14) after SCI with 17 mice in each group. All the groups received a moderate impacted spinal cord injury ex-cept the sham group. Evan's Blue (EB) was administered intraperitoneally to detect the permeability of BSCB. Occludin was analyzed by im-munofluorescence, the expressions of occludin and MMP-9 were detected by Western blotting. Results After SCI, BMS score significantly reduced, compared with S2 group, S14 group showed a significant increase (P<0.01). The permeability of BSCB was seriously damaged af-ter SCI. Compared with S2 group, S14 group showed a notable down-regulation in the permeability of injured micro-vessels (P<0.05). The expression of occludin was down-regulated and the expression of MMP-9 was up-regulated 7 days after SCI (P<0.05). Compared with S2 group, S14 group showed a significant up-regulation of occludin and a remarkable down-regulation of MMP-9 (P<0.05). Conclusion After SCI, MMP-9 might mediate the expression of occludin to influence the BSCB permeability.

The relationship between expression of Id-2 and MMP-9 and clinical pathology index in rectal cancer / 重庆医学

Objective To observe the expression level of inhibitor of differentiation 2 (Id‐2) and matrix metalloproteinases‐9 (MMP‐9) in rectal cancer ,analysis the correlation of the expression level of them ,to study the relationship between the expression level of them and the clinical pathology indicators of rectal cancer .Methods Rectal cancer tissues and normal tissue adjacent to rec‐tal cancer were obtained from the rectal cancer resection of 56 patients with rectal cancer ,using immunohistochemical method to ob‐serve the expression level of Id‐2 and MMP‐9 in normal tissue adjacent to rectal cancer and rectal cancer and Spearman correlation test to detect the correlation between the expression level of Id‐2 and MMP‐9 ;then we analyzed the relationships between the ex‐pression level of Id‐2 and MMP‐9 and the index of rectal cancer clinical pathology .Results The positive expression rate of Id‐2 in the in rectal cancer tissues is more higher than that of normal tissue of adjacent to rectal cancer (73 .21% vs .48 .21% ,P0 .05) .Conclusion There is a close relationship between the expression levels of Id‐2 and MMP‐9 in rectal cancer and the occurrence and development of rectal cancer .Rectal cancer with the higher Id‐2 expression level may be the ways to achieve tumor invasion and metastasis through MMP‐9 as a facilitator .

The relationship of ACS patients complicated with diabetes with carotid artery IMT, serum IL-18,MMP-9 and plasma Fib / 安徽医科大学学报

Objective To analyze the characteristic of some important clinical indicators, including carotid artery intima-middle thickness ( IMT) , peripheral blood Fib levels, serum IL-18 concentrations and serum MMP-9 con-centrations of acute coronary syndrome ( ACS) patients. On the other hand, to investigate the correlation among those indicators and major adverse cardiac events ( MACE) , and further to evaluate the value of those indicators in early prediction and prognosis judgement of ACS patients with diabetes( DM) in clinic. Methods This study en-rolled 120 ACS patients who had received coronary arteriography( CAG) examination. Among them, 60 cases had DM. Meanwhile, 60 cases who had DM were selected as DM group,60 cases of healthy people who received physi-cal health examination were selected as the control group. Carotid artery IMT was determined by color doppler ultra-sonography. The levels of Fib in peripheral blood were detected by solidification method. Immune turbidimetric method and ELISA were used to measure the concentrations of serum IL-18 and MMP-9 respectively. The CAG re-sults, complications and in-hospital mortality of ACS patients were also collected and analyzed. Results Carotid artery IMT, peripheral blood Fib levels, serum IL-18 concentrations and serum MMP-9 concentrations of ACS pa-tients were significantly increased compared with healthy control(P<0. 01). A comparison of those clinical indica-tors of ACS patients between with DM group and without 2 diabetes group showed a significant increase in ACS pa-tients with DM group. Carotid artery IMT, plasma Fib, serum IL-18, MMP-9 and Gensini score in ACS patients were positively correlated. The incidence of multi-vessel diseases of coronary artery was more frequent in ACS pa-tients with DM versus without DM ( 61. 7%) , while one or two vessel diseases of coronary artery was much more common in ACS patients without DM (61. 7%) . The Gensini score of ACS patients with DM group was much high-er than that of ACS patients without DM group ( P<0. 01 );severe and extremely severe lesions occurred more fre-quently in ACS patients with DM group (73. 3%) ,while mild-to-moderate lesions occurred more frequently in ACS patients without DM group (56. 7%) . Peripheral blood Fib levels, serum IL-18 and MMP-9 concentrations were significantly higher in ACS patients with MACEs compared to ACS patients without MACEs. Peripheral blood Fib levels, serum IL-18 concentrations and serum MMP-9 concentrations of ACS diabetes mellitus extended the down-ward trend with the treatment time after standardized treatment show time-effect relationship. Conclusion Carotid artery IMT, peripheral blood Fib levels, serum IL-18 concentration and serum MMP-9 concentrations have great po-tential to become effective clinical indicators, which could be used to quantitatively predict coronary atherosclero-sis,and further to determine the risk degree and short-term prognosis of ACS patients with DM.