Long noncoding RNAs HAND2-AS1 ultrasound microbubbles suppress hepatocellular carcinoma progression by regulating the miR-873-5p/tissue inhibitor of matrix metalloproteinase-2 axis

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.

A matrix metalloproteinase-responsive hydrogel system controls angiogenic peptide release for repair of cerebral ischemia/reperfusion injury

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.

Suppression of matrix metalloproteinase-2 via RNA interference inhibits pancreatic carcinoma cell invasiveness and adhesion

AIM:To investigate the inhibitory effects of RNA interference (RNAi) on expression of matrix metalloproteinase-2 (MMP-2) gene and invasiveness and adhesion of human pancreatic cancer cell line,BxPC-3.METHODS:RNAi was performed using the vector (pGPU6)-based small interference RNA (siRNA) plasmid gene silence system to specifically knock down MMP-2 expression in pancreatic cancer cell line,BxPC-3. Four groups of different specific target sequence in coding region of MMP-2 and one non-specific sequence were chosen to construct four experimental siRNA plasmids of pGPU6-1,pGPU6-2,pGPU6-3 and pGPU6-4,and one negative control siRNA plasmid of pGPU6 (-). MMP-2 expression was measured by reverse transcription polymerase chain reaction (RT-PCR) and Western blot. Cell proliferation and apoptosis were examined by methyl thiazolyl tetrazolium (MTT) and flow cytometry,respectively. The abilities of adhesion and invasion were detected by cell adhesion assay and cell invasion assay using Transwell chambers.RESULTS:The expression of MMP-2 was inhibited and the inhibitory effects of different sequence varied. pGPU6-1 group had the most efficient inhibitory effect,followed by pGPU6-2 and pGPU6-3 groups.Invasiveness and adhesion were more significantly reduced in pGPU6-1,pGPU6-2 and pGPU6-3 groups as compared with pGPU6 (-) and blank control groups. However,no difference concerning cell proliferation and apoptosis was observed after transfection between experiment groups and control groups.CONCLUSION:RNAi against MMP-2 successfully inhibited the mRNA and protein expression of MMP-2 in the pancreatic cancer cell line,BxPC-3,leading to a potent suppression of tumor cell adhesion and invasion without affecting cell proliferation and apoptosis. These findings suggest that the RNAi approach towards MMP-2 may be an effective therapeutic strategy for the clinical management of pancreatic tumor.

Relationship between matrix metalloproteinase-2 mRNA expression and clinicopathological and urokinase-type plasminogen activator system parameters and prognosis in human gastric cancer

AIM: To investigate the relationship between matrix metalloproteinase-2 (MMP-2) mRNA expression and clinicopathologic and urokinase-type plasminogen activator (uPA) system parameter and prognosis in human gastric cancer. METHODS: Expression of MMP-2 mRNA, uPA, and uPA-R mRNA in tumor tissues and ≥5 cm adjacent normal tissues from 67 cases of gastric cancer was studied using RT-PCR and Northern blot respectively.Survival analyses were done using the Kaplan-Meier method. RESULTS: The expression rates of MMP-2 mRNA,uPA and uPA-R mRNA in tumor tissues (31%,41%,and 51%, respectively) were significantly higher than those in ≥5 cm adjacent tissues (19%, 11%, and 9%; X2=4.59,43.58, and 53.24 respectively, P<0.05,0.0001,and 0.0001, respectively). Expression of MMP-2 mRNA was significantly correlated with lymph node metastasis (metastasis: 61.9%, no metastasis: 39.1%, X2= 7.61, P<0.05),Lauren's classification of diffuse/mixed types:54.2%,intestinal type: 26.3%,X2 = 4.25, P<0.05, expression of uPA and uPA-R mRNA (uPA+: 55.1%, uPA-: 22.2% and uPA-R+: 54.9%, uPA-R-: 18.8%, X2=5.72 and 6.40 respectively, P<0.05).Kaplan-Meier survival analysis of MMP-2 mRNA expression did not show significant difference in all 67 cases, but revealed an association of the expression of MMP-2 mRNA, uPA, and uPA-R mRNA with worse prognosis (P= 0.0083, 0.0160, and 0.0094, respectively). CONCLUSION: MMP-2 may play an important role in the development of invasion and metastasis of gastric cancer.

Correlation of RECK with Matrix Metalloproteinase-2 in Regulation of Trophoblast Invasion of Early Pregnancy

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.

Distribution and relative activity of matrix metalloproteinase-2 in human coronal dentin

The presence of matrix metalloproteinase-2 （MMP-2） in dentin has been reported, but its distribution and activity level in mature human coronal dentin are not well understood. The purpose of this study was to determine the MMP-2 distribution and relative activity in demineralized dentin. Crowns of twenty eight human molars were sectioned into inner （ID）, middle （MD）, and outer dentin （OD） regions and demineralized. MMP-2 was extracted with 0.33 mol·L-1 EDTA/2 mol·L-1 guanidine-HCl, pH 7.4, and MMP-2 concentration was estimated with enzyme-linked immunoabsorbant assay （ELISA）. Further characterization was accomplished by Western blotting analysis and gelatin zymography. The mean concentrations of MMP-2 per mg dentin protein in the dentin regions were significantly different （P=0.043）： 0.9 ng （ID）, 0.4 ng （MD）, and 2.2 ng （OD）, respectively. The pattern of MMP-2 concentration was OD〉ID〉MD. Western blotting analysis detected -66 and -72 kDa immunopositive proteins corresponding to pro- and mature MMP-2, respectively, in the ID and MD, and a -66 kDa protein in the OD. Gelatinolytic activity consistent with MMP-2 was detected in all regions. Interestingly, the pattern of levels of Western blot immunodetection and gelatinolytic activity was MD〉ID〉OD. The eoneentration of MMP-2 in human coronal dentin was highest in the region of dentin that contains the dentinoenamel junction and least in the middle region of dentin. However, levels of Western blot immunodetection and gelatinolytic activity did not correlate with the estimated regional concentrations of MMP-2, potentially indicating region specific protein interactions.

Vascular Endothelial Growth Factorl65-regulated Nasopharyngeal Carcinoma Cell Lines Invasion and Migration Involve Expression and Activation of Matrix Metalloproteinase-2

The effect of vascular endothelial growth factor （VEGF） overexpression on matrix metalloproteinase-2 （MMP-2） in nasopharyngeal carcinoma （NPC） cells in vitro and the possible mechanism involved were investigated, and the correlation between the expression of VEGF and MMP-2 in NPC evaluated. The NPC cells were transfected with PAd-trackVEGF165 plasmid. The expression levels of VEGF and MMP-2 mRNA and protein in NPC cells were detected by semi-quantitative RT-PCR and Western blot respectively. It was found that the expression of VEGF and MMP-2 mRNA and protein was significantly increased in NPC cells after transfection of VEGF 165. It was concluded that the expression of VEGF was correlated to the in vitro invasion of NPC cells, and the induction of MMP-2 by VEGF was a key process of NPC cell invasion.

Expressions of cyclooxygenase-2 and matrix metalloproteinase-9 in cervical carcinoma and their clinical significance

Objective: To investigate the expressions of cyclooxygenase (COX)-2 and matrix metalloproteinase (MMP)-9 in cervical carcinoma and their clinical significance. Methods: Immunohistochemistry SP method was used to detect the expres- sions of COX-2 and MMP-9 in 72 cases of invasive carcinoma of cervix (ICC) and 16 cases of normal cervical epithelium remote from tumor (NCE). The relationships between the expressions of COX-2, MMP-9 in ICC and some characteristics relating to clinical pathology of cervical carcinoma such as histological grading, lymph node metastasis, stromal invasion and FIGO stage were analyzed statistically. Results: The rates of the positive expressions of COX-2 and MMP-9 in ICC were significantly higher than those in NCE. COX-2: 88.9% (64/72) in group ICC and 12.5% (2/16) in group NCE, P = 0.000; MMP-9: 94.4% (68/72) in group ICC and 43.8% (7/16) in group NCE, P = 0.000. The expression of COX-2 was positively correlated with lymph node metastasis (r = 0.296, P = 0.012) and stromal invasion (r = 0.257, P = 0.029). The expression of MMP-9 was positively correlated with FIGO stage (r = 0.329, P = 0.005) and histological grading (r = 0.351, P = 0.003). The expression of COX-2 was positively correlated with the expression of MMP-9 in ICC (r = 0.297, P = 0.011). Conclusion: The overexpressions of COX-2 and MMP-9 were closely related to the invasion and growth of cervical carcinoma. The tissue with the overexpression of COX-2 had strong invasion ability. COX-2 and MMP-9 had synergistic effect on proliferation, invasion and metastasis of cancer cells. Detecting the coexpression of COX-2 and MMP-9 may be of value in further understanding the biological behavior and predicting the prognosis of cervical carcinoma.

不同程度冠脉病变冠心病患者血清亲环素A、可溶性生长刺激表达基因2蛋白、基质金属蛋白酶-29水平变化及其诊断价值分析

目的:分析不同程度冠脉病变冠心病患者血清亲环素A(CyPA)、可溶性生长刺激表达基因2蛋白(sST2)、基质金属蛋白酶-29(MMP-29)水平变化及其诊断价值。方法:收集60例冠心病患者作为冠心病组,另在同一时期内的体检人员中收集50例健康者作为对照组。其中冠心病组经冠脉造影检查后,根据病变类型分为三组,即不稳定心绞痛、稳定性心绞痛以及急性心肌梗死组;根据病变支数分为三组,即单支病变、双支病变以及三支病变组;根据Gensini评分分为三组,即轻度病变、中度病变以及重度病变组。比较观察组与对照组血清CyPA、sST2、MMP-29水平;比较不同疾病类型患者血清CyPA、sST2、MMP-29水平;比较不同病变支数患者血清CyPA、sST2、MMP-29水平;比较不同病变程度患者血清CyPA、sST2、MMP-29水平;分析冠心病患者血清CyPA、sST2、MMP-29水平与病变程度的相关性及诊断价值。结果:观察组血清CyPA、sST2、MMP-29水平高于对照组(均P<0.05);三组间血清CyPA、sST2、MMP-29水平比较差异有统计学意义,且与稳定性心绞痛组比较,不稳定性心绞痛组、急性心肌梗死组更高,而急性心肌梗死组比较不稳定性心较痛组也更高(均P<0.05);三组间血清CyPA、sST2、MMP-29水平比较差异有统计学意义,且双支病变组、三支病变组比较单支病变组更高,而三支病变组比较双支病变组也更高(均P<0.05);三组间血清CyPA、sST2、MMP-29水平比较差异有统计学意义,且与轻度病变组比较,中度病变组、重度病变组更高,而与中度病变组比较,重度病变组更高(均P<0.05);经Spearman相关性分析显示,冠心病患者血清CyPA、sST2、MMP-29检测值与其病变程度具有正相关关系(均P<0.05);经ROC曲线分析,血清CyPA诊断冠心病的曲线下面积(AUC)、特异度高于sST2和MMP-29(均P<0.05)。结论:冠心病患者血清CyPA、sST2、MMP-29水平越高,冠脉病变程度越严重,CyPA、sST2、MMP-29可作为冠心病病情诊断及评估的指标之一。

Rosiglitazone uppresses lipopolysaccharide-induced matrix metalloproteinase-2 activity in rat aortic endothelial cells via rasMEK1/2 signaling

ix metalloproteinase(MMPs) plays a key role in the pathogenesis of chronic inflammatory disease,such as atherosclerosis.Among MMPs,MMP-2 is regarded as a major proteinase in atherosclerotic plaque lesions.Peroxisome proliferator activated receptor-gamma(PPARg) ameliorates oxidative stress and the inflammatory response.The aim of the present study was to evaluate the effect of Rosiglitazone on Lipopolysaccharide(LPS)-induced MMP-2 activation as well as its possible mechanism.LPS-induced MMP-2 activity was inhibited by Rosiglitazone(PPARg agonist) in the rat aortic endothelial cells(RAEC).LPS-induced MMP-2 activation was diminished no matter exposure to NF-kB Activation Inhibitor II(JSH-23)or Ras inhibitor,farnesylthiosalicylic acid(FTS). Further study shows that LPS-induced activation of Phospho-Rho A and Phospho-MEKl/2 were significantly inhibited by Rosiglitazone.The activation of NF-kB p65 in the nuclear extract of cells was also significantly suppressed by Rosiglitazone, moreover,the expression of NF-κB p65 was partly activated by GW9662(PPARg antagonist).NF-kB DNA binding activity was also demolished by Rosiglitazone.In summary,our data showed that PPARg agonist,Rosiglitazone suppresses LPS-activated MMP-2 secretion via Ras-MEK1/2 signaling pathways and NF-kB activation.PPARg agonist and Ras-MEK1/2 pathway may be another potential therapeutic target for the disease induced by chronic inflammation.

Cryptotanshinone attenuates isoprenaline-induced cardiac fibrosis in the mouse associated with upregulation and activation of matrix metalloproteinase-2

Objectives The impairment of matrix metallopro- teinase-2(MMP-2)has been associated with the development of cardiac fibrosis.Although the Chinese herb Salvia miltior-rhiza has been widely used in patients with cardiovascular disorders,the mechanisms involved have not been elucidated. The purpose of the present study was to determine whether the administration of cryptotanshinone,an active ingredient of Salvia miltiorrhiza,could prevent the cardiac fibrosis induced by isoprenaline and to investigate the underlying mechanisms. Methods and Results Male C57BL/6 mice were submitted to receive daily injection of 0.9%saline,3 mg/kg isoprenaline, or isoprenaline plus 20 mg/kg cryptotanshinone by gastric gavage for 2 weeks.Herein,we demonstrate that cryptotanshinone can significantly ameliorate the isoprenaline-induced cardiac fibrosis,which was associated with marked up-regulation and activation of MMP-2 in ventricular myocardium. Additionally,we demonstrate that cryptotanshinone can dose-dependently upregulate and activate MMP-2 in cultured cardiac fibroblast.Moreover,incubation with cryptotanshinone also can prevent isoprenaline-induced downregulation and inactivation of MMP-2 in cultured cardiac fibroblast. Conclusions Taken together,our data suggest that cryptotanshinone may become a novel and potent antifibrotic agent. The present findings might further our understanding of the role of MMP-2 in cardiac fibrosis and antifibrotic mechanisms of cryptotanshinone.

Study on matrix metalloproteinase-2, 9 in peri-implant sulcular fluid

Objective: To study the expression of matrix metalloproteinases-2, 9 (MMP-2, MMP-9) of healthy implant and peri-implant sulcular fluid (PISF) by enzyme-linked immunosorbent assay (ELISA) method, and evaluate the level of MMP-2 and MMP-9 in sulcular fluid as an objective indicator of tissue inflammation around implants. Methods: A total of 40 implants were selected from 30 patients who were treated with dental implants and were divided into two groups: the inflammatory group and the healthy control group with 20 pieces respectively. ELISA double antibody sandwich method was used to detect the levels of MMP-2 and MMP-9 in PISF. Results: The MMP-2 and MMP-9 expressions were significantly different between the healthy implant group and the peri-implant group (p < .05). The concentration of MMP-2, MMP-9, and the amount of sulcular fluid in the inflammatory implant group were positively correlated with the clinical parameters (probing depth [PD], modified sulcus bleeding index [mSBI]). Conclusions: Under physiological conditions, the levels of MMP-2 and MMP-9 were low. When the periodontal tissue was stimulated by inflammation, the expression levels of MMP-2 and MMP-9 were increased, which could reflect the severity of inflammation. The increase levels of MMP-2 and MMP-9 in PISF could better reflect the health status of peri-implant tissues, which could be used as an objective indicator to assist in the diagnosis of peri-implant inflammation.

血清MMP-2、TNF-α及IL-17在脊柱结核患者预后中的价值研究

目的评价血清基质金属蛋白酶2(matrix metalloproteinase-2,MMP-2)、肿瘤坏死因子(tumor necrosis factor-α,TNF-α)、白细胞介素-17(interleukin-17,IL-17)在脊柱结核患者预后中的价值。方法选取2021年1月—2023年6月广州市胸科医院收治的60例脊柱结核患者为观察组,根据预后水平将其分为预后良好组(n=30)、预后不良组(n=30),并于同期选取30例健康体检者为对照组。对比分析观察组与对照组间、预后良好组与预后不良组间的血清MMP-2、TNF-α、IL-17水平差异。结果观察组患者的血清MMP-2(31.86±3.57)pg/mL、TNF-α(19.78±6.12)pg/mL、IL-17(40.18±6.40)pg/mL,高于对照组,差异有统计学意义(t=7.319、10.814、4.334,P<0.05)。预后不良血清组MMP-2、TNF-α、IL-17水平均高于预后良好组,差异有统计学意义(P<0.05)。结论脊柱结核患者的血清MMP-2、TNF-α、IL-17水平相较于健康人群会有明显的升高,且指标参数的上升情况与患者预后水平息息相关。

血清dp-ucMGP、BGP水平与2型糖尿病肾脏病变的相关性及预测价值

目的探讨去磷酸-未羧化基质GLA蛋白(dp-ucMGP)、骨钙素(BGP)水平与2型糖尿病肾脏病变(DKD)的相关性及预测价值。方法收集2020年9月~2021年11月在我院内分泌科住院的138例2型糖尿病(T2DM)患者,以尿微量白蛋白/肌酐(ACR)水平分组:ACR<3 mg/mmol为单纯糖尿病组(DM,n=56);ACR在3~30 mg/mmol为早期糖尿病肾脏病变组(eDKD,n=38);ACR>30 mg/mmol为临床糖尿病肾病组(cDKD,n=44);检测患者血中dp-ucMGP、BGP及临床生化指标。结果与DM组相比,eDKD组和cDKD组患者的dp-ucMGP升高,BGP降低(均P<0.05)。Spearman相关性分析结果显示dp-ucMGP与CRE、UREA、ACR水平呈正相关,与eGFR呈负相关(均P<0.05);BGP与ACR呈负相关(P<0.05);Logistic回归提示dp-ucMGP是DKD的危险因素,BGP是DKD的保护性因素。通过ROC曲线分析确定两者联合诊断DKD的敏感性0.781,特异性0.750,AUC是0.838(95%CI:0.773~0.902)。结论dp-ucMGP是DKD的危险因素,BGP是DKD保护因素,两者可能对DKD的诊断具有一定价值。

重型颅脑损伤病人血清NF-L和TIMP-2水平变化及临床意义

目的探讨重型颅脑损伤(TBI)病人血清神经丝蛋白轻链多肽(NF-L)、组织基质金属蛋白酶抑制因子-2(TIMP-2的水平变化及临床意义。方法2019年8月~2021年8月前瞻性收集重型TBI共122例,采用酶联免疫吸附试验检查入院血清NF-1和TIMP-2水平;伤后6个月,应用GOS评分评估预后,其中4~5分为预后良好,1~3分为预后不良。结果伤后6个月,预后良好72例,预后不良50例。预后不良组血清NF-L以及TIMP-2水平明显高于预后良好组(P<0.05)。入院血清NF-L水平(r=-0.585)、TIMP-2水平(r=-0.542)与入院GCS评分呈明显负相关(P<0.05)。多因素Cox回归分析显示,血清NF-L、TIMP-2水平增高是重型TBI伤后6个月预后不良的独立危险因素(P<0.05)。ROC曲线分析显示血清NF-L1≥54.60 pg/ml联合血清TIMP-2≥42.59 ng/ml预测重型TBI伤后6个月预后不良的曲线下面积为0.854(95%CI 0.789~0.919),灵敏度为82.0%,特异度为70.8。结论重型TBI病人血清NF-L、TIMP-2水平明显增高,是伤后6个月预后不良的危险因素;两者联合应用对病人预后具有较高的预测价值。

Imbalance of matrix metalloproteinase-9 and matrix metalloproteinase tissue inhibitor-1 may contribute to hemorrhage in cerebellar arteriovenous malformations

In this study, we determined the expression levels of matrix metalloproteinase-2 and -9 and matrix metalloproteinase tissue inhibitor-1 and -2 in brain tissues and blood plasma of patients undergoing surgery for cerebellar arteriovenous malformations or primary epilepsy （control group）. Immunohistochemistry and enzyme-linked immunosorbent assay revealed that the expression of matrix metalloproteinase-9 and matrix metalloproteinase tissue inhibitor-1 was significantly higher in patients with cerebellar arteriovenous malformations than in patients with primary epilepsy. The ratio of matrix metalloproteinase-9 to matrix metalloproteinase tissue inhibitor-1 was significantly higher in patients with hemorrhagic cerebellar arteriovenous malformations compared with those with non-hemorrhagic malformations. Matrix metalloproteinase-2 and matrix metalloproteinase tissue inhibitor-2 levels were not significantly changed. These findings indicate that an imbalance of matrix metalloproteinase-9 and matrix metalloproteinase tissue inhibitor-I, resulting in a relative overabundance of matrix metalloproteinase-9, might be the underlying mechanism of hemorrhage of cerebellar arteriovenous malformations.

All-trans retinoic acid regulates the expression of MMP-2 and TGF-β2 via RDH5 in retinal pigment epithelium cells

·AIM: To investigate the effect of all-trans retinoic acid(ATRA) on retinol dehydrogenase 5(RDH5), matrix metalloproteinase-2(MMP-2) and transforming growth factor-β2(TGF-β2) transcription levels, and the effect of RDH5 on MMP-2 and TGF-β2 in retinal pigment epithelium(RPE) cells.·METHODS: After adult RPE cell line-19(ARPE-19 cells) intervened with gradient concentrations of ATRA(0-20 μmol/L) for 24h, flow cytometry was used to detect the proliferation and apoptosis of cells in each group, and quantitative realtime polymerase chain reaction(q RT-PCR) was used to detect RDH5, MMP-2 and TGF-β2 m RNA expression. Then, after ARPE-19 cells transfected with three different si RNA targets for 48h, the RDH5 knockdown efficiency of each group and expression of MMP-2 and TGF-β2 m RNA within them was detected by q RT-PCR. ·RESULTS: Flow cytometry results showed that ATRA could inhibit the proliferation of RPE cells and promote the apoptosis of RPE cells, and the difference of apoptosis was statistically significant when the ATRA concentration exceeded 5 μmol/L and compared with the normal control group(P=0.027 and P=0.031, respectively). q RT-PCR results showed that ATRA could significantly inhibit the expression level of RDH5 m RNA(P<0.001) and promote the expression of MMP-2 and TGF-β2 m RNA(P=0.03 and P<0.001, respectively) in a dose-dependent manner, especially when treated with 5 μmol/L ATRA. The knockdown efficiency of RDH5 si RNA varies with different targets, among which RDH5 si RNA-435 had the highest knockdown efficiency, i.e., more than 50% lower than that of the negative control group(P=0.02). When RDH5 was knocked down for 48h, the results of q RT-PCR showed that the expressions of MMP-2 and TGF-β2 m RNA were significantly up-regulated(P<0.001).·CONCLUSION: ATRA inhibits the expression of RDH5 and promotes MMP-2 and TGF-β2, and further RDH5 knockdown significantly upregulates MMP-2 and TGF-β2. These findings suggest that RDH5 may be involved in an epithelial-mesenchymal transition of RPE cells mediated by ATRA.

急性冠脉综合征患者血清白介素-6、基质金属蛋白酶2、CD40配体的水平变化及临床意义

目的探究急性冠脉综合征患者血清白介素-6、基质金属蛋白酶2、CD40配体的水平变化及临床意义。方法选取2020年1月至10月厦门市第三医院心血管内科收治的50例急性ST段抬高型心肌梗死患者作为STEMI组,50例非ST段抬高型急性冠脉综合征患者作为NST-ACS组,另同期选择50名健康体检者作为对照组。比较三组的血清白介素-6、基质金属蛋白酶2、CD40配体水平。结果STEMI组血清白介素-6、基质金属蛋白酶2、CD40配体的水平均高于NST-ACS组、对照组,差异有统计学意义(P<0.05)。联合检测的阳性检出率高于其他单一指标,差异有统计学意义(P<0.008)。结论对急性冠脉综合征患者血清白介素-6、基质金属蛋白酶2、CD40配体的水平变化进行检测,能够对患者病变程度进行评价,利于后续治疗的开展,值得研究和推广。

胃癌组织高迁移率族蛋白A2与基质金属蛋白酶-9表达与肿瘤侵袭转移的关系及预后意义

目的探讨胃癌组织中高迁移率族蛋白A2(HMGA2)及基质金属蛋白酶-9(MMP-9)表达与肿瘤侵袭和转移能力的关系及预后意义。方法采用免疫组化法(SP法)检测93例胃癌组织、30例正常胃黏膜组织中HMGA2、MMP-9的表达;收集患者临床病历资料,并进行随访。结果 HGMA2蛋白在胃癌组织中阳性表达率分别为明显高于正常胃黏膜(P<0.01);MMP-9蛋白在胃癌组织中阳性表达率明显高于正常胃黏膜(P<0.01)。HMGA2与MMP-9在胃癌组织中的蛋白阳性表达均与胃癌组织的肿瘤浸润深度、肿瘤分化程度、淋巴结转移、TNM分期有关(P<0.05);与患者的性别、年龄、肿瘤直径无关(P>0.05)。相关性分析发现,HMGA2与MMP-9在胃癌组织中的表达情况呈正相关(r=0.317,P<0.01)。经Kaplan-Meier生存分析显示,HMGA2、MMP-9蛋白表达阳性患者的生存率均低于表达阴性患者(P<0.01)。结论 HMGA2、MMP-9与胃癌浸润和转移有关,两者表达具有相互协同作用,对胃癌的侵袭和转移起重要的促进作用。HMGA2、MMP-9是影响预后的危险因素,可能成为胃癌治疗的新靶点。