Serum Levels Of MMP-9 Research Articles

The prognostic value of serum MMP-7 levels in prostate cancer patients who received docetaxel, abiraterone, or enzalutamide therapy

ObjectivesThe rapidly changing treatment landscape in metastatic castration-resistant prostate cancer (mCRPC) calls for biomarkers to guide treatment decisions. We recently identified MMP-7 as a potential serum marker for the prediction of response and survival in mCRPC patients who received docetaxel (DOC) chemotherapy. Here, we aimed to test this finding in an independent patient cohort and in addition to explore the prognostic potential of serum MMP-7 in abiraterone (ABI) or enzalutamide (ENZA) treated patients. Methods and MaterialsMMP-7 levels were measured in 836 serum samples from 320 mCRPC patients collected before and during DOC (n = 95), ABI (n = 140), or ENZA (n = 85) treatment by using the ELISA method. Results were correlated with clinical and follow-up data. ResultsMMP-7 baseline levels were similar between the 3 treatment groups. In the ABI and ENZA cohorts, baseline MMP-7 levels were lower in patients with prior radical prostatectomy (P = 0.058 and P = 0.041, respectively). Baseline MMP-7 levels above the median were associated with shorter overall survival for the DOC (P = 0.001) and ENZA (P = 0.006) cohorts. Multivariable analyses in the DOC and ENZA cohorts revealed that high pretreatment MMP-7 level is an independent risk factor for patients’ survival. In addition, in DOC-treated patients with high baseline MMP-7 level, marker decrease at the third DOC cycle was associated with improved survival. Patients with high baseline MMP-7 levels had better survival when treated with ABI compared to DOC or ENZA. ConclusionsWe confirmed the prognostic value of pretreatment MMP-7 serum level and its changes as independent predictors of survival in DOC-treated mCRPC patients. In addition, high MMP-7 was a negative predictor in ENZA-treated but not in ABI-treated patients. These results warrant further research to confirm the predictive value of serum MMP-7 and to explore the potential mechanistic involvement of MMP-7 in DOC and ENZA resistance of mCRPC patients.

Pathological features of established osteoarthritis with hydrathrosis are similar to rheumatoid arthritis

The prevalence of rheumatoid arthritis (RA) and knee osteoarthritis (OA) is increasing with our aging society. Some reports suggest that OA with effusion synovitis develops into RA and early OA patients with effusion are pathologically similar to those with RA. The purpose of this study was to examine the relationship between histological features of established knee OA with or without effusion and RA. Seventy-nine patients in which synovial specimens were obtained during total knee arthroplasty were included. Patients were divided into an RA group, OA with effusion (OA+) group, and OA without effusion (OA-) group. The Rooney synovitis score and serum matrix metalloproteinase (MMP)-3 levels were compared among groups. We also examined the correlation between the Rooney synovitis score and its sub-scores with MMP-3 levels. The total Rooney score was significantly higher in the RA group than in the OA+ and OA- groups (25.4 vs 17.1, p < 0.01; 25.4 vs 13.5, p < 0.001, respectively). This score also was significantly higher in the OA+ group than in the OA- group (p < 0.05). The proliferating blood vessels score, perivascular infiltrates of lymphocytes score, focal aggregates of lymphocytes score, and diffuse infiltrates of lymphocytes score were significantly higher in the RA group than in the OA- group (7.05 vs 3.29, 4.95 vs 3.43, 3.29 vs 1.46, and 2.26 vs 1.18, respectively; p < 0.05), but not compared with the OA+ group. The total Rooney score demonstrated a significantly positive correlation with serum MMP-3 levels in the RA group (r = 0.61; 95% CI: 0.28 to 0.81; p < 0.01) and in the OA+ group (r = 0.57; 95% CI: 0.24 to 0.78; p < 0.01). Previous reports showed the histological similarity between RA and early OA with effusion. We confirmed this histological similarity, in particular the distribution of lymphocytes, between RA and established OA with effusion. It is possible that cases diagnosed as OA with effusion might progress to overt RA. • Histological similarity was observed between RA and established OA with effusion.

High Expression of MMP-9 in Primary Tumors and High Preoperative MPO in Serum Predict Improved Prognosis in Colorectal Cancer with Operable Liver Metastases

Introduction: The liver metastases of colorectal cancer (CRC) can be surgically treated in selected cases, with continuously improving results. Matrix metalloproteinases (MMPs) contribute to cancer invasion by degrading the extracellular matrix, and elevated levels of MMP-2, MMP-8, and MMP-9 have been detected in several malignancies. Myeloperoxidase (MPO) is a mediator of tissue damage that can oxidatively activate latent MMPs. We evaluated the prognostic value of MMP-2, MMP-8, and MMP-9 in tissue samples of primary tumors and liver metastases and the pre- and postoperative serum levels of MMP-8, MMP-9, and MPO in CRC patients undergoing liver resection. Methods: Tissue and serum samples were obtained from 111 patients who had primary colorectal tumors and their liver metastases surgically treated at the Helsinki University Hospital between 1988 and 2007. Tissue expression of MMP-2, MMP-8, and MMP-9 in primary tumors and liver metastases was evaluated by immunohistochemistry. Pre- and postoperative serum concentrations of MMP-8, MMP-9, and MPO were determined using a time-resolved immunofluorometric assay or commercially available enzyme-linked immunosorbent assay kits. Clinical data were retrieved from patient records and the Central Statistical Office of Finland. Associations with disease-free survival (DFS) and overall survival (OS) were estimated using Cox regression analysis and the Kaplan-Meier method. Results: High expression of MMP-9 in colorectal tumor tissue was associated with better DFS (p = 0.010), and high preoperative MPO in serum with improved DFS and OS (p < 0.001 and p = 0.014, respectively). The prognostic significance varied according to gender, age, and the synchronicity of liver metastases. Conclusion: Low preoperative MPO in serum might identify patients at high risk of recurrence and death after resection of colorectal liver metastases. Elevated preoperative MPO and high expression of MMP-9 in colorectal tumor tissue indicate an improved prognosis. The use of these biomarkers should be adjusted according to clinical characteristics.

Evaluation of Serum Interleukin-10 and Matrix Metalloproteinase-9 Levels as Predictors of Glycemic Alteration in Type 2 Diabetes Mellitus in Patients with Periodontitis

Purpose: The present study was conducted to evaluate serum interleukin-10 and MMP-9 levels as predictors of glycemic alteration in type 2 Diabetic patients with periodontitis. Subjects and methods: This study was conducted on thirty (30) patients that were divided into two groups: Group 1 fifteen (15) patients with type 2 diabetes and periodontitis; Group 2 fifteen (15) patients with type 2 diabetes and c periodontitis receiving adjunctive treatment Omega-3 and aspirin. Elisa kit was used to evaluate the concentration of serum Mmp-9 and IL-10. Results: There was a statistically significant difference between (Group 1) and (Group 2) in the serum level of Mmp-9 (P-value 0.028) (P-value 0.010) after 3m and 6m as well as the serum level of IL-10(P-value 0.020) (P-value 0.029). Conclusion: Serum IL-10 can be used as predictor of glycemic alteration in type 2 Diabetes Mellitus.Omega-3 can be used as adjunctive treatment in periodontal disease.

The expression levels of Mir-146b and Mir-221 in thyroid carcinoma tissues and their correlation with malignancy degree

This experiment aimed to investigate the correlation between the expressions of mir-146b and mir-221 and the proliferation, invasion, and malignancy of tumor cells. For this purpose, 135 patients with thyroid cancer treated in our hospital and 120 patients with non-malignant thyroid cancer in the outpatient clinic were selected as subjects. Fine needle biopsy tissues of the two groups were taken as samples to detect the expression levels of mir-146b and mir-221 in the tissues. The effect of the two microRNA on the proliferation and migration of cancer cells was observed by the transfection of cell lines. The contents of gal-3 and MMP9 in serum were further detected, and their relationship with the expressions of mir-146b and mir-221 was analyzed. The results showed that the expressions of mir-146b and mir-221 were significantly decreased and increased in thyroid carcinoma fine-needle aspiration tissues. Mir-146b inhibited the proliferation and migration of cancer cells, while mir-221 promoted this process. In the more cancer cells, the expression levels of these two genes changed more, and the serum levels of gal-3 and MMP9 also increased. It was concluded that the expression levels of mir-146b and mir-221 were correlated with the degree of tumor malignancy, and the low expression of mir-146b and the high expression of mir-221 were correlated with the proliferation, invasion, and malignancy of thyroid cancer tumor cells.

The Behavior of MMP-2, MMP-7, MMP-9, and Their Inhibitors TIMP-1 and TIMP-2 in Adenoma-Colorectal Cancer Sequence

Background: We and others have previously shown that matrix metalloproteinases (MMPs) play a role in colorectal cancer (CRC) invasion and metastasis. However, the serum changes of various MMPs and their inhibitors (TIMPs) have scarcely been concomitantly investigated in identical blood samples in the normal colon-adenoma-CRC sequence. Methods: The MMP-2, MMP-7, MMP-9, TIMP-1, and TIMP-2 serum antigen concentrations were determined concomitantly in 19 tumor-free control patients, 19 patients with high-risk colorectal adenoma, and 47 patients with CRC by ELISA technique. The analyzed parameters were also investigated in correlation with CRC stages. Statistical analysis with one-way ANOVA and Student’s t test was performed. p values <0.05 were considered significant. Results: Serum antigen levels of MMPs and TIMPs were significantly increased in patients with CRC and adenomas compared to controls (mean values, ng/mL) (MMP-7: 5.88, 4.44, and 2.89, respectively, p = 0.001; MMP-9: 1,075.81, 999.22, and 845.97, respectively, p = 0.01; TIMP-1: 241.80, 205.98, and 166.53, respectively, p = 0.001; TIMP-2: 83.40, 80.30, and 69.62, respectively, p = 0.01). The elevated serum MMP-7, MMP-9, TIMP-1, and TIMP-2 levels significantly correlated with advanced tumor stages (p < 0.05). No statistically significant differences were observed in MMP-2 levels. Conclusions: We demonstrate that serum antigen concentrations of MMP-7, MMP-9, TIMP-1, and TIMP-2 were significantly increased in patients with CRC and adenomas compared to controls. These results suggest that MMPs and their inhibitors TIMP-1 and TIMP-2 play an important role in CRC invasion; however, they are also activated in premalignant adenomas. Furthermore, MMP-7, MMP-9, TIMP-1, and TIMP-2 may have a potential prognostic impact in CRC.

The Effect of Eccentric Resistance Training with and Without Blood Flow Restriction on Serum IL6 and MMP9 Levels in Young Active Men

Background: It has been assumed that during and after BFR exercises, many blood factors are activated and angiogenesis response is stimulated in the arteries. Objectives: Therefore, the current study aimed to determine the effect of two eccentric resistance training methods with and without blood flow restriction on serum IL6 and MMP9 levels in active young men. Methods: In this quasi-experimental study, 16 healthy men with a mean age of 27.8 ± 2.85 (years), the weight of 79.4 ± 12.4 (kg), and a body mass index of 25.5 ± 3.7 (kg/m2) were randomly assigned to either low-intensity eccentric group with BFR or the high-intensity eccentric without BFR. The high-intensity (70% - 80% maximum voluntary contraction MVC) eccentric exercise without BFR included 3 - 5 cycles of eccentric contraction of the quadriceps muscles, up to exhaustion, whereas low-intensity eccentric exercise executed similar exercise modality at intensity of 20% - 30% MVC with blood flow restriction up to exhaustion. Blood samples were taken from antecubital both before and after the exercise to measure serum IL6 and MMP9 values using the ELISA method. Data were analyzed using paired t-test and analysis of variance with repeated measure test in SPSS version 22. A P value of &lt; 0.05 was defined as statistically significant. Results: High-intensity resistance per se and low-intensity resistance exercise with BFR similarly resulted in a non-significant reduction of IL-6 and elevated levels of MMP-9 serum levels in active young men. Conclusions: Overall, the results indicated that a low-intensity resistance exercise session with restricted blood flow and a high-intensity resistance exercise without blood flow restriction equally did not affect IL6 and MMP9 serum of active young men. Further studies are needed to clarify the exact exercise modality that sufficiently stimulates angiogenesis.

Comparison of Serum Matrix Metalloproteinase-9 Value in Spondylitis Tuberculous with Degenerative Spine Disease

AIM: We aimed to compare the expression of MMP-9 in TB spondylitis using serum levels in the blood of patients suffering from TB spondylitis and compared to the control group.&#x0D; METHODS: Fourteen subjects were divided into two groups, with seven subjects of spondylitis tuberculous (TB) and seven subjects of degenerative spine disease (DSD) in the period from December 2017 to November 2018, who were included in the inclusion criteria included in this study and blood sampling was taken for examination of serum matrix metalloproteinase (MMP)-9 levels.&#x0D; RESULTS: There were significant differences in serum MMP-9 levels between spondylitis TB (ST) and DSDs with a significance value of 0.002 (p &lt; 0.05) with low serum MMP-9 levels in the ST study group 1857.14 ± 377.96 and mean in the control group 857.14 ± 243.97. There were significant differences in serum MMP-9 levels between ST and DSDs with a significance value of 0.002 (p &lt; 0.05) with low serum MMP-9 levels in the ST study group 1857.14 ± 377.96 and mean in the control group 857.14 ± 243.97.&#x0D; CONCLUSION: Patients suffering from ST have higher serum MMP-9 levels than patients with DSD, although MMP-9 is not a specific marker examination for ST, the results of this study can be suggestive into that can help to evaluate enzyme activity in patients with ST diseas

TNM staging for GIT cancers is correlated with the level of MMPs and TGF-β1.

Gastrointestinal (GIT) cancers represent the third common cancers worldwide, characterized by rapid progression and higher mortality rate. Matrix metalloproteinases (MMPs) play an important role in cancer metastases. The present study was conducted to estimate and evaluate the role of MMP-7, -9, -10 and -12 and TGF β1 along with conventional biomarkers (CEA and CA19-9) in gastric (GC), pancreatic (PC) and colorectal cancer (CRC) staging system according to tumor size (T), included lymph node (N) and metastasis (M). Seventy-five patients were divided into GC group (n = 25), PC group (n = 25), CRC group (n = 25) and twenty-five healthy subjects (control group). Serum levels of MMP-7, -10 and -12 were assayed simultaneously using luminex multiplex technique. Also, MMP-9, TGF-β1, CA19-9 and CEA were determined by ELISA. MMP-7,-9,-10, -12, TGF-β1 and CEA levels were significantly (p < 0.001) higher in GIT cancer groups compared with control. CA19-9 was significantly (p < 0.001) higher in PC and CRC groups compared with control. MMP-9 was positively correlated with TNM staging in PC patients. MMP-12 was negatively correlated with T in PC and positively correlated with M in CRC group. CA 19-9 was positively correlated with M grade in CRC. Depending on the estimated cutoff values of area under receiver curve; CA19-9 and MMP-7 were excellent diagnostic markers in PC, CEA and MMP-7 were excellent in CRC, and MMP-7 and MMP-9 were excellent in GC. Our findings indicated the clinical utility of MMPs in diagnosis and TNM staging of GIT cancers along with CEA and CA19-9.

Clinical value of matrix metalloproteinase-2 and -9 in ultrasound-guided radiofrequency ablation treatment for papillary thyroid carcinoma.

ObjectiveThis study aimed to investigate serum matrix metalloproteinase (MMP)-2 and MMP-9 levels in patients with papillary thyroid carcinoma (PTC).MethodsForty-one patients with PTC undergoing ultrasound-guided radiofrequency ablation (RFA) and 56 controls were included. Serum MMP-2 and MMP-9 levels were determined by enzyme-linked immunosorbent assay before and after surgery. Potential affecting factors were evaluated by logistic regression analysis.ResultsSerum MMP-2 and MMP-9 levels were significantly higher in PTC patients compared with controls, and decreased significantly after surgery. According to receiver operating characteristic curve analysis, diagnostic values for preoperative serum MMP-2 and MMP-9 levels were 82.4% and 86.6%. There was no contrast-agent perfusion in the ablation zone in 88.5% of lesions, and enhancement within or at the lesion edge in 11.4%. The volume reduction at 3 months’ follow-up was >40%. Age, microcalcification, irregular shape, and lesion diameter and number were influencing factors for PTC. Age, and lesion diameter and number were independent risk factors, while calcification and morphology were protective factors.ConclusionSerum MMP-2 and MMP-9 levels have important clinical values for the diagnosis and treatment of PTC by RFA. Preoperative serum MMP-2 and MMP-9 levels, combined with other affecting factors, contribute to disease prognosis.

Relationship between 3D Power Doppler Ultrasound and Serum MMP-2 and Ang-2 Levels in Pregnant Women with Preeclampsia.

To explore the relationship between 3D power Doppler ultrasound (3D-PDU) and serum MMP-2 and Ang-2 levels in pregnant women with preeclampsia (PE). Comparative analytical study. The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, China, from October 2017 to January 2020. One hundred and thirty-four pregnant women with PE were selected as the research subjects, with 67 cases in mild group and 67 cases in severe group. Sixty-seven healthy primigravidas were selected as normal control group. Serum MMP-2 and Ang-2 were detected. All subjects underwent prenatal 3D-PDU examination, and VI, FI and VFI were measured. Compared to normal control group, serum MMP-2 and Ang-2 levels of mild group and severe group decreased successively (all p <0.001); VI, FI, and VFI of mild group and severe group decreased successively (both p <0.001). Pearson correlation analysis showed that serum MMP-2 in pregnant women with PE was positively correlated with VI, FI, VFI (r = 0.940, p <0.001, r = 0.938, p <0.001, and r = 0.921, p <0.001, respectively); and serum Ang-2 was positively correlated with VI, FI, VFI (r = 0.958, p <0.001; r = 0.960; p <0.001; r = 0.945, p <0.001, respectively). 3D-PDU has a certain application value in the diagnosis of pregnant women with PE, variation tendency of VI, FI and VFI detected by 3D-PDU is closely associated with serum MMP-2 and Ang-2 levels. Key Words: Preeclampsia, Pregnant women, MMP-2, Ang-2, 3D power Doppler ultrasound (3D-PDU).

Effects of Dingkun Dan combined with Western medicine on endometrial β-catenin, VEGF and MMP-9 mRNA expression in rats with multiple lesions

The aim of this paper was to investigate the effect of Dingkun Dan on endometrial receptivity in rats with multiple lesions. Forty SD female rats with regular sexual cycle were randomly divided into 5 groups, control group, model group, progynova group, Dingkun Dan group and combination group. The thin endometrium model of kidney-yang deficiency was established in all the other rats except normal control group. The rats in normal control group were free to drink and eat; the rats in the model group were administered with distilled water; the rats in the progynova group were treated with progynova; rats in Dingkun Dan group were treated with Dingkun Dan, and the rats in combination group were treated with Dingkun Dan and progynova. After 15 days, serum levels of OPN, VEGF and MMP-9 were measured by ELISA. HE staining, immunohistochemistry and RT-PCR were used to analyze endome-trial morphology, endometrial thickness and the treatment mechanism of Dingkun Dan. As compared with the control group, the serum levels of OPN, VEGF and MMP-9 in the model group were significantly increased(P&lt;0.01). As compared with the model group, the serum levels of OPN and MMP-9 were decreased in Dingkun Dan group(P&lt;0.05, P&lt;0.01). As compared with the control group, endometrial stromal cells were fewer, the endometrium glands and blood vessels were sparse, and the endometrium was thinner significantly in the model group(P&lt;0.01). As compared with the model group, there were more endometrial glands, rich intimal vessels, and dense stromal cells in various treatment groups, and the endometrium were thickened significantly in the treatment groups(P&lt;0.01). As compared with the control group, the expression area of CK19 in the model group was decreased significantly(P&lt;0.01). As compared with the model group, the expression area of CK19 in each treatment group was increased significantly(P&lt;0.05). As compared with the control group, endometrial β-catenin and MMP-9 mRNA expression levels were increased significantly in the model group(P&lt;0.05), while VEGF mRNA expression was decreased(P&lt;0.05). As compared with the model group, MMP-9 mRNA expression was decreased significantly in the progynova group and the combination group(P&lt;0.05). Dingkun Dan combined with progynova can improve endometrial receptivity by up-regulating expression of β-catenin, VEGF mRNA and down-regulating the expression of MMP-9 mRNA in the injury rats.

Effects of sevoflurane inhalation anesthesia on IL-6, TNF-α and MMP-9 expression and hemodynamics in elderly patients undergoing lobectomy for lung cancer

Objective of current research was to investigate the effect of sevoflurane inhalation anesthesia on hemodynamics and inflammatory response in elderly patients with lung cancer lobectomy. Methods: A total of 168 patients with lung cancer who underwent lobectomy in our hospital from January 2019 to December 2019 were selected as the study subjects. The patients were divided into an observation group and control group according to the anesthesia program. In the control group, 1 mg/kg propofol intravenous pump induced anesthesia was maintained at 6mg/kg/h. In the observation group, 8% sevoflurane was used to induce anesthesia and 2% sevoflurane was used to maintain anesthesia. Mean artery pressure (MAP), heart rate (HR) and blood oxygen saturation (SpO2) were monitored at the beginning of single-lung ventilation (t1), when single-lung ventilation was changed to double-lung ventilation (t2), and at 30 minutes after double-lung ventilation (t3), respectively. Serum levels of interleukin-6 (IL-6), tumor necrosis factor (TNF-α), and matrix metalloproteinases (MMP-9) were measured using an enzyme-linked immunosorbent assay (ELISA) kit. Assess the patient's adverse reactions. Results: At time t1 and time t2, there was no significant difference in the three hemodynamic indicators between the two groups (P&gt;0.05). However, at t3, both MAP and HR in the observation group were significantly lower than those in the control group, while SpO2 was significantly higher than those in the control group (P&lt;0.05). At t1 and t2, there was no significant difference in IL-6 and TNF- levels between the two groups, but at t3, IL-6 and TNF-α levels in the observation group were significantly lower than those in the control group (P&lt;0.05). Compared with the control group, serum MMP-9 level was significantly decreased in the whole t1 to t3 stage (P&lt;0.05). The incidence of complications in the observation group was significantly higher than that in the control group. It was calculated that Sevoflurane can significantly improve hemodynamics and inflammatory response in elderly patients with lung cancer lobectomy, but the incidence of complications is high.

Abstract 552: Bradykinin Receptor B1/ Matrix Metalloprotease 3 Pathway is a Novel Target in Preventing Cardiac Ischemia-reperfusion Injury

Introduction: Impaired endothelial function leads to the progression of heart failure after Ischemia-reperfusion (IR). Kinin activation of bradykinin receptor 1 (B1R), a G protein-coupled receptor that has been found to induce capillary leakage, may serve as a critical mediator in cardiac microvascular barrier dysfunction. However, the underlying mechanisms are not clear. We found that B1R inhibition abolished IR-induced endothelial matrix metalloprotease (MMP3) expression and improved endothelial barrier formation. Thus, we hypothesized that B1R antagonist protects against cardiac IR injury through an MMP3 pathway. Methods and Results: MMP3-/- mice and their littermate controls (WT) were subjected to either cardiac IR or sham control. The baseline characteristics of these mice showed minimal phenotypes. Cardiac function was determined at 3, 7 and 24 days post-IR by echocardiography. The MMP3-/- mice displayed improved cardiac function compared to the control mice, as determined by fractional shortening (26% ± 1.1 MMP3-/- vs. 21% ± 0.9 WT, p&lt;0.05, n=5) and ejection fraction (48% ± 1.9 MMP3-/- vs. 42% ± 2.8.1 WT, p&lt;0.05, n=5), and treating with B1R antagonist (300 μg/Kg) significantly reduced serum MMP3 levels (p&lt;0.01). Compared to the control mice, MMP3-/- mice had significantly less infarction/area at risk 24 hours post-IR demonstrated through TTC staining. In vitro studies revealed that cellular hypoxia-reoxygenation (HR) injury significantly increased both B1R and MMP3 expression levels in primary isolated cardiac mice microvascular endothelial cells (mCMVEC). MMP3 levels were measured via ELISA. Moreover, B1R agonist treatment (1uM) increased MMP3 levels, while the use of the antagonist attenuated the increase of MMP3 in response to HR. Finally, the use of B1R antagonist improved MMP3 induced endothelial barrier dysfunction, which was measured by the electric cell-substrate impedance sensing (ECIS) system. Taken together, the results demonstrated that B1R antagonist abolished IR induced MMP3 induction and that the deletion of MMP3 is protective of cardiac function upon IR injury. Conclusions: MMP3 is a critical regulator of cardiac microvascular barrier function, and B1R/MMP3 could potentially serve as a novel therapeutic target for heart failure in response to IR injury.

A Randomized, Triple-blind Placebo-controlled Trial to Determine the Effect of Saffron on the Serum Levels of MMP-9 and TIMP-1 in Patients with Multiple Sclerosis.

Matrix metalloproteinases (MMP)-9 facilitates the migration of T-cells to central nervous system (CNS), while tissue inhibitor of metalloproteinases-1(TIMP-1) inhibits the function of MMP-9. This study aimed to determine the appropriate treatment option for multiple sclerosis (MS). Forty-three relapsing-remitting MS (RRMS) patients were randomly divided into two groups of 22 (group A, placebo) and 21 (group B, Saffron pill) individuals. Serum samples were collected from patients' blood before using the Saffron pills/placebo pills and then after 12 months. The serum level of MMP-9 and its inhibitor, as well as TIMP-1, were measured by ELISA kits. MMP-9 serum levels noticeably decreased in patients with MS following 12 months of treatment with Saffron pills (p=0.006) while the changes were not significant before and after 12 months of treatment with placebo pills. Although the levels of TIMP-1 increased significantly after one year treating with Saffron pills (p=0.0002), a considerable difference was not observed before and after taking the placebo pills. The study finding revealed that 12-months treatment with Saffron could have a significant role in reducing the serum level of MMP-9 and increasing the serum level of TIMP-1 in RRMS patients. Therefore, modulating the serum levels of MMP-9 as an important regulator of T cell trafficking to the CNS might be a promising strategy in the treatment of MS patients.

Effects of oxiracetam combined with ginkgo biloba extract in the treatment of acute intracerebral hemorrhage: A clinical study.

PurposeThe present clinical study was conducted to investigate the effect of oxiracetam combined with ginkgo biloba extract in treating patients with acute intracerebral hemorrhage.MethodsNinety‐eight patients with acute cerebral hemorrhage admitted to our hospital were divided into three groups. The differences of brain edema and cerebral hemorrhage were compared between the three groups after 1 and 2 weeks of treatment, and the recovery of neurological function, serum inflammatory factors, AQP‐4, MMP‐9, cognitive function, activities of daily living, and adverse reactions were compared between the three groups after 2 weeks of treatment.ResultsThere was no significant difference among the three groups before treatment (p > .05). After treatment, the recovery of neurological function, serum inflammatory factors, AQP‐4, MMP‐9 levels, cognitive function, and activities of daily living were improved. Among them, the neurological function recovery, serum inflammatory factors, AQP‐4, MMP‐9 levels, cognitive function, and activities of daily living in the combined treatment group and the control group elicited greater results than those in the routine group. The results of the combined treatment group showed the most significant difference (p < .05). The concentration of IL‐6 decreased from 135.98 ± 12.54 to 91.83 ± 7.69 pg/ml, AQP‐4 from 227.55 μg/L ± 21.06 to 114.31 ± 9.22 μg/L, and MMP‐9 from 172.39 ± 9.81 to 94.98 ± 5.01 ng/ml. In addition, the neurological function recovery, the levels of serum inflammatory factors, cognitive function, and activities of daily living in the combined treatment group were better than those in the control group (p < .05). The mean score of MRS in the combined treatment group decreased from 3.36 ± 0.98 at admission to 1.91 ± 0.38.ConclusionOxiracetam combined with Ginkgo biloba extract in the treatment of acute cerebral hemorrhage has a significant improvement effect.

Correlation of MMP-9 and HMGB1 expression with the cognitive function in patients with epilepsy and factors affecting the prognosis

This study was designed to investigate the expressions and roles of MMP-9 and HMGB1 in peripheral blood of patients with epilepsy and their relationship with the cognitive function and to explore factors affecting the prognosis of epilepsy patients. A total of 127 patients with epilepsy were collected in the study group and 120 healthy subjects receiving a physical examination at the same time were collected in the control group. The MMP-9 and HMGB1 expressions and their diagnostic value for epilepsy were compared between the two groups. The relationship between MMP-9 and HMGB1 expression levels and the clinical-pathological features and the Mini-mental State Evaluation Scale (MMSE) of patients from the study group were also analyzed. The serum levels of MMP-9 and HMGB1 in the study group were significantly higher than those in the control group (P&lt; 0.001), and were greatly decreased after the treatment (P&lt;0.001). The ROC curve showed that MMP-9 and HMGB1 combined detection had a good diagnostic efficiency for epilepsy. MMP-9 was much related to the type and disease duration of epilepsy (P&lt; 0.05). HMGB1 was significantly associated with disease duration, seizure, and previous treatment history of epilepsy (P&lt; 0.050). According to the Pearson correlation coefficient analysis, the expressions of MMP-9 and HMGB1 were negatively correlated with MMSE scores of the study group (P&lt; 0.001). Logistic regression analysis showed that the duration of disease, seizures, MMP-9, and HMGB1 were independent risk factors for the prognosis of epilepsy. The expression levels of MMP-9 and HMGB1 in peripheral blood of patients with epilepsy are significantly increased, and negatively correlated with neurological function scores. They have potential involvement in the occurrence and development of epilepsy, which makes them significant for the diagnosis and treatment of epilepsy in the future.

THU0109 DOES HIGH BASELINE LEVEL OF MATRIX METALLPROTEINASES 3 (MMP3) INDICATE MORE MTP5 JOINT EROSIONS IN EARLY RHEUMATOID ARTHRITIS PATIENTS? (THE 2-YEAR PROSPECTIVE ULTRASONOGRAPHIC STUDY)

Background:The serum MMP3 level is considered biomarker which reflects local inflammation of joints and correlates with joint damage progression in early rheumatoid arthritis (1).Objectives:To investigate the association of high baseline MMP3 serum levels with bone erosion finding at the level of typical location for rheumatoid arthritis (RA) in patients with early, treatment “naïve” RA, who has no radiographic visible erosions, using ultrasound method (US).Methods:Sixty-three pts. (9 males and 54 females; mean age 53.4 yrs 21-81 ± 14.1) with early RA according to EULAR/ACR 2010 criteria and symptom duration of ≤12 months (mean duration of 3.8 months) had baseline serum MMP3 levels tested. Serum levels of soluble MMP3 were performed blindly, without knowledge of the US data at the basal visit only, using the recommended normal cut-off range (a level above normal was rated as positive). Patients had been DMARDs/glucocorticoid naïve, with no visible X-ray erosions at the study entry. The lateral, dorsal and posterior part of styloid, MCP2, MCP5 and MTP5 joints of both side, were analyzed for presence of bone erosion (yes/no), according to OMERACT US group definition, using high frequency linear probe by ESAOTE My Lab 70 machine at baseline visit and after 24 months.Results:The 50 pts completed follow-up. 46 pts. had basal serum MMP3 level higher than normal (MMP3 +, mean value 185.1±241.0). US bone erosions were present in 55/63 (87.3%) pts, most often in MTP5 joints, both at the study entry and after 24 months of follow up (25 pts-39.6% and 32 pts-64% respectively). At baseline visit no significant difference was found between a group of MMP3+ and MMP3- pts. regarding to US bone erosion presence at the level of all analyzed joints (styloid process: 12 MMP3+/4 MMP3- pts.; p=0.836; MCP2: 14 MMP3+/6 MMP3- pts., p=0.713; MCP5:8 MMP3+/0 MMP3- pts, p=0.06; MTP5: 26 MMP3+/11 MMP3- pts, p=0.55). After 24 months, significant difference was found between a group of MMP3+ and negative pts for MTP5 US bone erosions finding (33 MMP3+/ 6 MMP3- pts, p=0.03) only, (styloid process:21 MMP3+/5 MMP3- pts, p=0.623; MCP2: 26 MMP3+/7 MMP3- pts, p=0.851, MCP5: 14 MMP3+/2 MMP3- pts, p=0.266).Conclusion:In our group of RA patients without initial X-ray changes, the high baseline serum level of MMP3 was significantly correlated with new MTP5 bone erosions by US after 2-year of follow-up.

Leucine-rich alpha-2 glycoprotein 1, high mobility group box 1, matrix metalloproteinase 3 and annexin A1 as biomarkers of ulcerative colitis endoscopic and histological activity.

The LRG, HMGB1, MMP3 and ANXA1 proteins have been implicated in different inflammatory pathways in ulcerative colitis (UC), but their role as specific biomarkers of both endoscopic and histological activity has yet to be elucidated. In the present study, we aimed to evaluate the LRG1, HMGB1, MMP3 and ANXA1 as potential serum biomarkers for UC endoscopic and histological activity. This cross-sectional study included UC patients under 5-ASA, and healthy controls (HC) undergoing colonoscopy. Blood and biopsy samples were obtained and endoscopic Mayo sub-score (Ms) was recorded for the UC patients. Intramucosal calprotectin as a marker of histologic activity was evaluated in all biopsy samples and serum LRG1, HMGB1, MMP3 and ANXA1 levels were measured in the blood samples. The HCs ANXA1 level was lower compared to that of the UC group [P = 0.00, area under the curve (AUC) = 0.881] and so was the HCs MMP3 level compared to that of patients (P = 0.00, AUC = 0.835). The HCs ANXA1 levels were also lower compared to these of the independent Ms groups, even to the Ms = 0 (P = 0.00, AUC = 0.913). UC endoscopic activity was associated with MMP3 levels (r = 0.54, P = 0.000) but not with ANXA1, LRG1 and HMGB1 levels CONCLUSION: Serum ANXA1 is a potential diagnostic biomarker of UC and serum MMP3 is a potential biomarker of UC endoscopic and histological activity.

Serum Levels of Matrix Metalloproteinase-1 in Brazilian Patients with Benign Prostatic Hyperplasia or Prostate Cancer.

Metalloproteinases (MMPs) are involved in metastatic tumor processes, with changes in circulating levels detected in several cancer types. Here, we compare serum concentrations of metalloproteinase-1 (MMP-1) across individuals clinically diagnosed with prostate cancer (PCa) or benign prostatic hyperplasia (BPH), correcting results for the rs495366 single nucleotide polymorphism (SNP) that predisposes to differential MMP-1 levels. 196 men aged ≥50 years were followed at a university hospital urology outpatient clinic, with clinical, anthropometric, and rectal examinations performed by one urologist. Blood samples obtained prior to any clinical intervention provided baseline MMP-1 and total/free PSA levels as well as metabolic, hormonal, and inflammatory markers. The SNP was genotyped by real-time PCR. Participants with medical and/or laboratory profile compatible with malignancy composed the PCa group when confirmed by the Gleason scale. As expected, A-allele homozygotes showed reduced levels of MMP-1. Genotype-adjusted analyses revealed the mean MMP-1 level as 2-fold higher in PCa carriers compared to BPH patients. No other differences were found according to the prostatic condition or genotypic distribution, except for the expected raise in total and free PSA levels in PCa. In conclusion, increased serum levels of MMP-1 were observed in this context of prostatic malignancy compared to a benign phenotype, regardless of a genetic influence.