Serum MMP-9 Research Articles

The Role of Serum Matrix Metalloproteinase - 9 as a Prognostic Biomarker for Short-Term Outcome in Acute Ischemic Stroke

The Role of Serum Matrix Metalloproteinase - 9 as a Prognostic Biomarker for Short-Term Outcome in Acute Ischemic Stroke

Mendelian Randomization Study of the Relationship Between Serum Matrix Metalloproteinases and the Occurrence of Sepsis

BackgroundObservational studies have shown that matrix metalloproteinases (MMPs) are associated with sepsis. However, it is unknown whether this association represents a causal relationship.MethodsMendelian randomization (MR) analysis was conducted to assess the potential causal role of circulating MMPs in sepsis. Single nucleotide polymorphisms (SNPs) associated with circulating MMPs levels were used as instrumental variables (IVs). In a sepsis genome-wide association study comprising 1573 cases and 454,775 European ancestry controls, we examined these IVs' effects using a two-sample MR study. Causal estimates were calculated using inverse variance weighting (IVW), the weighted median method, and MR-Egger analysis.ResultsGenetically predict that MMP-1 (OR = 1.011, 95% CI 0.772–1.325, p = 0.936), MMP-3 (OR = 1.036, 95% CI 0.862–1.244, p = 0.707), MMP-7 (OR = 1.206, 95% CI 0.960–1.515, p = 0.108), MMP-8 (OR = 1.041, 95% CI 0.949–1.144, p = 0.395), MMP-9 (OR = 1.101, 95% CI 0.831–1.458, p = 0.503), MMP-10 (OR = 1.028, 95% CI 0.840–1.260, p = 0.789) was not associated with the risk of sepsis.ConclusionsThe MR study does not provide evidence that circulating levels of MMPs (1, 3, 7, 8, 9, 10) were the causes of sepsis.

Serum matrix metalloproteinase-7: a potential biomarker in patients with Lynch Syndrome.

The expression of tissue and serum matrix metalloproteinase-7 (MMP-7) was shown to be elevated both in colon cancer and dysplastic lesions. We aimed to evaluate, for the first time, its role as a diagnostic marker in Lynch syndrome (LS) carriers, a hereditary syndrome with predisposition to colon cancer. This was a case control study. Baseline serum MMP-7 levels were determined by ELISA in 40 colon cancer patients, 62 LS-carriers and 60 healthy controls. Retrieved data from medical files included demographics, background diseases, clinical data regarding tumor characteristics and genetic data. We assessed the association of serum MMP-7 levels with different variables in the study cohort using linear regression model adjusted for potential confounders. In crude analysis, serum MMP-7 levels were significantly higher in colon cancer group compared to LS-carriers and controls [median (IQR) 4.1 ng/ml (2.7-6.0), 2.3 ng/ml (1.7-3.1), 2.5 ng/ml (1.5-3.7), respectively; p value - p < 0.001) while there was no difference between the two last groups (p value = 0.583). However, after adjusting for age and gender, LS-carriers' patients had 18% higher concentrations of serum MMP-7 compared to healthy controls (p value = 0.037), while colon cancer patients had 50% higher serum MMP-7 level in comparison to healthy controls (p value < 0.001). Additionally, age was positively associated with higher serum MMP-7 levels across all study groups (r = 0.67, p value < 0.001). In contrast, no correlation was observed between serum MMP-7 and either tumor staging and gene mutation. Age-adjusted serum MMP-7 levels in asymptomatic LS carriers are higher than its levels in healthy population. While in colon cancer, MMP-7 higher level probably reflects the tumor burden and may have a prognostic effect, its significance and clinical applicability as a biomarker for tumorigenesis in LS is less clear and should be elucidated.

Elevated blood and cerebrospinal fluid biomarkers of microglial activation and blood‒brain barrier disruption in anti-NMDA receptor encephalitis

BackgroundAnti-NMDA receptor (NMDAR) encephalitis is an autoimmune disease characterized by complex neuropsychiatric syndrome and cerebrospinal fluid (CSF) NMDAR antibodies. Triggering receptor expressed on myeloid cells 2 (TREM2) has been reported to be associated with inflammation of the central nervous system (CNS). Matrix metalloproteinase-9 (MMP9) and cluster of differentiation (CD44) were measured to evaluate blood‒brain barrier (BBB) permeability in anti-NMDAR encephalitis. The roles of microglial activation and BBB disruption in anti-NMDAR encephalitis are not well known.FindingsIn this work, we detected increased expression levels of CSF sTREM2, CSF and serum CD44, and serum MMP9 in anti-NMDAR encephalitis patients compared with controls. CSF sTREM2 levels were positively related to both CSF CD44 levels (r = 0.702, p < 0.0001) and serum MMP9 levels (r = 0.428, p = 0.021). In addition, CSF sTREM2 levels were related to clinical parameters (modified Rankin Scale scores, r = 0.422, p = 0.023, and Glasgow Coma Scale scores, r = − 0.401, p = 0.031).ConclusionIncreased sTREM2 levels in CSF as well as increased CD44 and MMP9 in serum and CSF reflected activation of microglia and disruption of the BBB in anti-NMDAR encephalitis, expanding the understanding of neuroinflammation in this disease. The factors mentioned above may have potential as novel targets for intervention or novel diagnostic biomarkers.

Contrast-Enhanced Computed Tomography and Laboratory Parameters as Non-Invasive Diagnostic Markers of Pancreatic Fibrosis.

Pancreatic fibrosis (PF) is a part of the pathogenesis in most pancreatic disorders and plays a crucial role in chronic pancreatitis development. The aim of our study was to investigate a relationship between PF grade and signs in resected pancreatic specimens, and the results of both multidetector computed tomography (MDCT) post-processing parameters and fibronectin (FN), hyaluronic acid (HA), matrix metalloproteinase (MMP)-1, and MMP-9 serum levels. The examination results of 74 patients were analyzed. The unenhanced pancreas density (UPD) value and contrast enhancement ratio (CER) showed statistically significant differences in groups with peri- and intralobular fibrosis grades, an integrative index of fibrosis, inflammation in pancreatic tissue, and pancreatic duct epithelium metaplasia, while the normalized contrast enhancement ratio in the venous phase (NCER VP) significantly differed with the perilobular fibrosis grade, integrative fibrosis index, and inflammation (p < 0.05). The blood FN level showed a weak positive correlation with the intralobular fibrosis grade (rho = 0.32, p = 0.008). The blood level of HA positively correlated with the presence of prominent and enlarged peripheral nerves (rho = 0.28, p = 0.02) and negatively correlated with the unenhanced pancreas density value (rho = -0.42, p = 0.0001). MMP-1 and MMP-9 values' intergroup analysis and correlation did not show any statistical significance. The UPD value, NCER VP, and CER, as well as blood levels of FN and HA, could be used in non-invasive PF diagnosis.

Diagnostic values of MMP-9 and TGF-1β in assessing the severity of liver fibrosis and the rate of its progression in patients with chronic hepatitis C GT 1 infection

Aim. The purpose of our work is to find out diagnostic values of serum MMP-9 and TGF-1β determination for assessing the severity of liver fibrosis and the rate of its progression in patients with chronic hepatitis C genotype 1 (CHC GT1) infection. Materials and methods. 92 patients with CHC GT1 were examined. The severity of liver fibrosis was assessed by elastometry. The rate of liver fibrosis progression was calculated using the T. Poynard formula. Serum levels of TGF-1β and MMP-9 were measured by ELISA method. Results. In patients with CHC GT1, the most noticeable changes in the serum parameters of fibrogenesis / fibrinolysis were observed in the presence of F 3–4. The probability of liver fibrosis stages F 3–4 was high at the serum levels of TGF-1β &gt;12.03 pg/ml (p &lt; 0.001), MMP-9 ≤987.20 pg/ml (p = 0.016), TGF-1β/MMP-9 ratio &gt;0.011 (p &lt; 0.001). Fast liver fibrosis progression was more often registered in F 3–4 than in F 0–2 (62.9 % vs. 16.7 %, p &lt; 0.0001). Increasing rate of liver fibrosis progression in these patients was confirmed by a higher ratio of TGF-1β/MMP-9 compared to that in patients with a slow rate of liver fibrosis progression (p &lt; 0.05). The probability of fast liver fibrosis progression was high at the serum levels of TGF-1β &gt;8.69 pg/ml (p &lt; 0.001), MMP-9 ≤920.65 (p = 0.005), TGF-1β/MMP-9 ratio &gt; 0.011 (p &lt; 0.001). Conclusions. The diagnostic value of MMP-9 and TGF-1β in assessing the liver fibrosis severity and the rate of its progression in patients with CHC GT1 has been defined. Cut-off levels of MMP-9, TGF-1β and the TGF-1β/MMP-9 ratio for stratification of patients with severe liver fibrosis and the fast rate of its progression have been proposed.

Effects of low-dose ketamine infusion on vascular endothelial growth factor and matrix metalloproteinase-9 among patients with treatment-resistant depression and suicidal ideation

BackgroundEvidence indicates that vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) influence the pathophysiology of depression. However, whether low-dose ketamine regulates VEGF and MMP-9 levels and whether changes in VEGF and MMP-9 levels are associated with the antidepressant and antisuicidal effects of ketamine remained unclear. MethodsForty-eight patients with treatment-resistant depression and strong suicidal ideation (TRD-SI) were randomly assigned to a single infusion of 0.5-mg/kg ketamine or 0.045-mg/kg midazolam. The Montgomery–Åsberg Depression Rating Scale (MADRS) and Columbia-Suicide Severity Rating Scale–Ideation Severity Subscale (CSSRS-ISS) were used at baseline and subsequently at several postinfusion timepoints. VEGF and MMP-9 serum levels were analyzed at baseline and on day 3 postinfusion. ResultsAfter adjustment for baseline levels, no significant differences in VEGF (p = .912) and MMP-9 (p = .758) levels were identified on day 3 postinfusion between the study groups. Baseline VEGF levels but not MMP-9 levels were negatively associated with MADRS and CSSRS-ISS scores following infusion. DiscussionA single infusion of low-dose ketamine did not alter the VEGF and MMP-9 levels of the patients with TRD-SI. Higher baseline VEGF levels were associated with greater antidepressant and antisuicidal effects of single low-dose ketamine infusion.

The correlation between serum matrix metalloproteinase-9 levels and the severity of coronary artery stenosis in patients with acute coronary syndrome

Link of Video Abstract: https://www.youtube.com/watch?v=mzVt00YaibkIntroduction: Atherosclerosis causes coronary artery stenosis in a lot of patients with acute coronary syndrome (ACS). By controlling platelet activity and destroying the extracellular matrix, a group of enzymes known as matrix metalloproteinases (MMPs) contribute to the plaque rupture process that causes ACS. The study aimed to determine whether there was any correlation between the amount of serum MMP-9 and the severity of coronary artery stenosis in ACS patients. Methods: Cross-sectional analytical observational design was employed in this investigation. The research population consisted of ACS patients at the Dr. Zainoel Abidin General Hospital in Banda Aceh, Indonesia. Patients who were included as samples had to satisfy the inclusion and exclusion requirements. This study used analysis of variance (ANOVA) as a bivariate analysis to examine the connection between blood MMP-9 levels and the severity of coronary artery stenosis. The threshold for statistical significance was a p-value≤0.05. Results: This research comprised 40 patients with ACS, of which 14 had STEMI, 11 had NSTEMI, and 15 had unstable angina pectoris (UAP). Eleven individuals had mild coronary artery stenosis, eleven had moderate stenosis, and eighteen had severe stenosis, according to an analysis of the Gensini score. Bivariate analysis revealed no significant relationship between blood MMP-9 levels and the degree of coronary artery stenosis in ACS patients (p-value = 0.434). Conclusions: In patients with ACS at the Dr. Zainoel Abidin General Hospital in Banda Aceh, Indonesia, there was no statistically significant association between serum MMP-9 levels and the degree of coronary artery stenosis, according to this study.

Interleukin-38: A crucial player in periodontitis.

The objective of this study was to compare the levels of gingival crevicular fluid (GCF), salivary, and serum matrix metalloproteinase-9, interleukin (IL)-17, IL-36γ, and IL-38 in individuals with healthy periodontium, gingivitis, and periodontitis and to evaluate their correlations with clinical periodontal parameters. Ninety systemically healthy and nonsmoking volunteers divided into a healthy (H) group (n = 30), a gingivitis (G) group (n = 30), and a periodontitis (P) group (n = 30) were included in this study. Clinical periodontal parameters of volunteers were recorded, and GCF, unstimulated saliva, and serum samples were collected. Data analysis was done with enzyme-linked immunosorbent assays. The Kruskal-Wallis test and Bonferroni correction were used for multiple comparisons and post hoc statistical analyses. The group H had significantly lower clinical parameters than the group P (p < 0.001). GCF and salivary IL-36γ and IL-38 levels were significantly higher in the group P than in the H and G groups (p < 0.05). Positive correlations between biochemical findings and clinical periodontal parameters were observed. IL-36γ and IL-38 levels in GCF, saliva, and serum correlate with clinical periodontal parameters and may play a role in determining the activity of periodontitis.

Association of Circulating Matrix Metalloproteinase-9 and the Risk of Coronary Heart Disease in Young Smokers

Introduction: Smoking causes cardiovascular risk which may alter the stability between the production and degradation of the extracellular matrix. Matrix metalloproteinase-9 (MMP-9) is a zinc-containing endopeptidase that degrades the extracellular matrix and plays a vital role in tissue remodeling. As a result, elevated serum MMP-9 levels produced by smoking, particularly at young age, raise the risk of future CHD. So this study aims to find out the possible relationship between circulating MMP-9 and the risk of cardiovascular disease in young smokers. Methods: The study was conducted on smokers with CHD subjects attending cardiology and medicine OP of the SRM Medical College Hospital and research center Tamil Nadu, India. The study group was divided into three groups. Group 1 includes 120 healthy controls as nonsmokers, Group 2 includes 120 smokers with Coronary heart disease (CHD), and Group 3 includes 120 smokers with diabetes and CHD subjects in the age group of 20-55 years. Serum MMP-9, hs-CRP, and APO-E levels were measured using the ELISA method and the lipid level was measured enzymatically using AU480 automatic analyzer (back man coulter). Results: The mean serum MMP-9, hs-CRP, and APO-E levels were significantly higher in both groups (p&lt;0.05) when compared to controls. The study also shows a significant positive association between MMP-9 with hs-CRP, APO-E, smoking burden, and smoking intensity. Conclusion: The study concludes a significant association exists between cigarette smoking with MMP-9 and also relative exposure to circulating inflammation markers plays a potential role in the pathogenesis of CHD.

Bee Honey Extract Attenuates Hyperglycemia in Induced Type 1 Diabetes: Impact of Antioxidant and Angiogenesis Activities on Diabetic Severity In Vivo

Background: Diabetes mellitus (DM) has become a disease prevalent worldwide. Honey, which comprises predominantly bioactive constituents, has anti-inflammatory, antioxidant, and immunomodulating properties. Aim: Recent developments and benefits of natural products in treating various diseases have caught the attention of researchers. This study aims to investigate the antidiabetic effect of bee honey extract on induced diabetic Swiss mice. Materials and Methods: Fifty Swiss male mice were randomly assigned to five groups of 10 mice each. Group I served as the negative control; in group II, the mice received 2 mg/kg/b.wt of honey extract only; and groups III, IV, and V received cyclosporine (CsA) (20 mg/kg/day, s.c.) daily for 10 days prior to receiving streptozotocin (STZ) inoculated at multiple low doses (MLDSTZ) (30 mg/kg/day, i.p.) for five consecutive days. Group IV was administered with insulin initiated at a dose of 0.5 U/kg/b.wt as a standard treatment (positive control). Group V was administered 2 mg/kg/b.wt of honey extract, while group III received no treatment. Results: The results showed a significant hypoglycemic effect, increased body weight, increased liver glycogen levels, and the amelioration of antioxidant activities in groups IV and V compared with the diabetic group III. Moreover, serum matrix metalloproteinase (MMP-9) concentrations were significantly reduced in the mice treated with the insulin and honey extract in groups IV and V and the tissue inhibitor metalloproteinase-1 (TIMP-1) levels were significantly higher than the serum levels in group III. Furthermore, the histopathological examination of groups IV and V revealed regenerative changes with the restoration of normal islet cell architecture, as compared to the diabetic mice in group III. Compared to group I, group II showed no changes and exhibited non-significant data. Conclusion: Honey extract plays an effective role in improving all biomarkers in treated group V. Furthermore, MMP-9 and TIMP-1 are considered prognostic markers in the progression, severity, diagnosis, and treatment of type 1 DM. This may play an important role for the treatment of individuals in the future.

The role of matrix metalloproteinases and their tissue inhibitors in the formation of hypertrophic skin scars with the use of a pulsed dye laser and Fermencol phonophoresis

BACKGROUND: An imbalance between matrix metalloproteinases (MMPs) expression and tissue inhibitors of MMP is considered as a possible mechanism for impaired collagen synthesis and degradation, which leads to the development of hypertrophic scars. The use of a vascular laser, in particular a pulsed dye laser, leads to coagulation of the vascular locus that feeds the hypertrophic skin scar, resulting in a decrease in extracellular matrix synthesis. The use of collagenase phonophoresis increases the effectiveness of laser therapy due to the destruction of the extracellular matrix.&#x0D; AIM: To study the role of matrix metalloproteinases and their tissue inhibitors in the pathogenesis of immature hypertrophic skin scars and to evaluate the dynamics of enzymes during the combined use of a pulsed dye laser and Fermenkol phonophoresis.&#x0D; MATERIAL AND METHODS: The study was performed with the participation of 125 patients aged 22 to 55 years with immature (up to 6 months) hypertrophic skin scars. All patients were divided into 4 groups according to the simple fixed randomization procedure. The first group (control, n=32) received course local compression therapy using silicone plates for 2 months. The second group (main group I, n=31) underwent two courses of Fermencol phonophoresis (5 daily procedures lasting 10 minutes each with a break of 34 weeks). The third group (main group II, n=31) underwent two pulsed dye laser procedures with an interval of 4 weeks. The fourth group (main III, n=31) received complex treatment, which included a combination of two pulsed dye laser procedures and two cycles of Fermenkol phonophoresis. The study of the clinical condition of patients was carried out according to the modified Vancouver scar scale (VSS). The content of MMP and tissue inhibitor of metalloproteinase-1 in blood serum was determined by enzyme immunoassay. Patients were examined twice: before the start and 2 weeks after the end of the course of treatment. To form a sample of reference values of MMPs and tissue inhibitors of metalloproteinases (TIMPs), a group of 20 somatically healthy individuals was used.&#x0D; RESULTS: Initially reduced levels of MMP-1 and MMP-9 were found in the blood serum of patients with immature hypertrophic skin scars, with high values of TIMP-1, which allows us to consider reduced expression as an important link in the pathogenesis of the fibroproliferative process in the skin, which causes excessive deposition of extracellular matrix components. The use of pulsed dye laser in combination with Fermencol phonophoresis was accompanied by an increase in the content of MMP in the blood serum of patients with immature hypertrophic skin scars, which positively correlated with the severity of the clinical result of treatment, assessed by VSS.&#x0D; CONCLUSION: A conclusion was made about the clinical and pathogenetic significance of MMPs and TIMPs in the development of fibroplastic processes, which allows us to consider these biochemical parameters as informative criteria for the effectiveness of the therapy.

Comparative Study of the Pain, Function, and Biomarkers of Joint Disease in the Transition to Adulthood in Individuals With and Without Cerebral Palsy.

Biomarkers have potential to identify early signs of joint disease. This study compared joint pain and function in adolescents and young adults with cerebral palsy compared with individuals without. This cross-sectional study compared individuals with cerebral palsy ( n = 20), aged 13-30 yrs with Gross Motor Function Classification System I-III and age-matched individuals without cerebral palsy ( n = 20). Knee and hip joint pain measured using Numeric Pain Rating Scale and Knee injury and Osteoarthritis Outcome Score and Hip dysfunction and Osteoarthritis Outcome Score surveys. Objective strength and function were also measured. Biomarkers for tissue turnover (serum cartilage oligomeric matrix protein, urinary C-terminal crosslinked telopeptide of type II collagen) and cartilage degradation (serum matrix metalloproteinase 1, matrix metalloproteinase 3) were measured in blood and urinary samples. Individuals with cerebral palsy had increased knee and hip joint pain, reduced leg strength, reduced walking and standing speeds, and ability to carry out activities of daily living ( P < 0.005) compared with controls. They also had higher serum matrix metalloproteinase 1 ( P < 0.001) and urinary C-terminal crosslinked telopeptide of type II collagen levels ( P < 0.05). Individuals with cerebral palsy who were Gross Motor Function Classification System I and II demonstrated reduced hip joint pain ( P = 0.02) and higher matrix metalloproteinase 1 levels ( P = 0.02) compared with Gross Motor Function Classification System III. Individuals with cerebral palsy with less severe mobility deficits had higher matrix metalloproteinase 1 levels likely due to more prolonged exposure to abnormal joint loading forces but experienced less joint pain.

Effect of Doxycycline on Progression of Arterial Calcification in the Noninvasive Treatment of Abdominal Aortic Aneurysm Clinical Trial (N-TA(3)CT)

Doxycycline has been shown to prevent arterial calcification via attenuation of matrix metalloproteinases (MMP) in preclinical models. We assessed the effects of doxycycline on progression of arterial calcification in patients enrolled in the Non-Invasive Treatment of Abdominal Aortic Aneurysm Clinical Trial (N-TA3CT). Two hundred and sixty-one patients were randomized to 100 mg doxycycline twice daily or placebo. Arterial calcification was measured in abdominal vessels on noncontrast computed tomography scans. Patients with baseline computed tomography scan and 1 or more follow-up scans within the 2-year study were included for analysis. For individual arteries, mean change in iliofemoral artery calcification over time was calculated via linear regression. Serum MMP-3 and MMP-9 levels were measured at baseline and 6months. Sixty-five patients in the doxycycline and 66 in the placebo arm were included in this analysis. Baseline characteristics between the groups were similar. The unadjusted mean change in iliofemoral calcium score per year trended toward higher values in patients treated with doxycycline compared with placebo (322±399 units/year vs. 217±307 units/year, P=0.09). After 6months, changes in serum MMP-3 and MMP-9 levels were not significantly different between study arms. In patients with small aortic aneurysm, treatment with doxycycline 100 mg twice daily did not decrease circulating levels of the matrix degrading enzymes MMP-3 and 9 or alter the progression of arterial calcification.

Analysis of MMP-2-735C/T (rs2285053) and MMP-9-1562C/T (rs3918242) Polymorphisms in the Risk Assessment of Developing Lung Cancer

Matrix metalloproteinase (MMP)-2 and -9 are gelatinases which are capable of degrading type IV collagen and have been linked to cancer invasion and metastatic development. MMP-2 and MMP-9 gene polymorphisms may affect their biological function, and thus their role in cancer development and progression. We analyzed the association of the polymorphism frequencies of MMP-2-735C/T and MMP-9-1562C/T with MMP-2 and MMP-9 serum concentrations, as well as their potential effects in lung cancer patients. We conducted a retrospective, case-control study consisting of 112 lung cancer patients and 100 healthy individuals from a Caucasian population in Poland. Polymerase chain reaction with restriction fragment length polymorphism (PCR/RFLP) and electrophoresis was used to genotype genomic DNA from whole blood samples. MMP-2 and MMP-9 serum concentrations were then determined using ELISA. For statistical analysis, Statistica version 13 from TIBCO Software Inc. was utilized with a significance level &lt;0.05. Logistic regression analysis revealed that MMP-2-735CC (OR = 5.39; 95% CI = 0.62–47.17; p = 0.238504) and -735CT genotype (OR = 7.22; 95% CI = 0.78–67.14; p = 0.072836), as well as MMP-9-1562CC (OR = 1.45; 95% CI = 0.31–6.70; p = 0.757914) and -1562CT genotype (OR = 1.60; 95% CI = 0.33–7.83; p = 0.548801) were associated with a higher risk of lung cancer. There were statistically significant differences observed in the MMP-2 concentration between individuals with the -735CC genotype and the -735CT genotype (non-smoking control: 204.04 ng/mL vs. 237.00 ng/mL, respectively, p = 0.041479; adenocarcinoma patients: 157.69 ng/mL vs. 126.37 ng/mL, respectively, p = 0.013222), as well as differences in the MMP-9 concentration between individuals with the -1562CC genotype and the -1562CT genotype (smoking control: 385.67 ng/mL vs. 562.80 ng/mL, respectively, p = 0.000936; patients with other lung neoplasms: 821.64 ng/mL vs. 928.88 ng/mL, respectively p = 0.023315). The role of MMP-2-735C/T and MMP-9 -1562C/T polymorphisms in an increased risk of lung cancer cannot be dismissed. Specific genotypes affect MMP-2 and MMP-9 concentrations in both lung cancer patients and healthy controls, which may thereby increase lung cancer risk, disease aggressiveness, and patient survival outcomes.

Characteristics of persistent arthritis with refractory Kawasaki disease: a single-center retrospective study

Arthritis is one complication of Kawasaki disease (KD); however, the clinical features of arthritis in KD have not been well clarified. We retrospectively investigated the characteristics of persistent arthritis beyond the subacute phase of KD. In this cohort, 49 of 243 patients (20%) developed arthritis, with 33 patients (14%) experiencing persistent arthritis. Among these 33 patients, 31 (94%) had complete KD. Thirty (91%) were resistant to first intravenous immunoglobulin, and 15 (45%) required additional infliximab. Five patients (15%) developed coronary artery lesions, and 24 (73%) had oligoarthritis, mainly in large lower-extremity joints. Twenty-four patients (73%) complained of arthralgia. At arthritis onset, 16 patients (48%) presented with fever, including recurrent fever in 10 patients. Serum C-reactive protein concentration in patients with active arthritis significantly increased compared with after acute KD treatment (2.4 vs. 0.7 mg/dL, p < 0.001). Serum matrix metalloproteinase-3, a biomarker of arthritis, was significantly higher in patients with active arthritis than in remission (93.7 vs. 20.3 ng/mL, p < 0.001). Thirty (91%) and 14 (42%) patients, respectively, were treated with non-steroidal anti-inflammatory drugs and prednisolone, and they completely recovered. To summarize, persistent arthritis is a common complication in refractory KD, and adequate diagnosis and treatment are necessary.

PRSS2 regulates EMT and metastasis via MMP-9 in gastric cancer

Serine protease 2 (PRSS2) is upregulated in gastric cancer tissues, correlates with poor prognosis and promotes migration and invasion of gastric cancer cells. However, the exact mechanism by which PRSS2 promotes metastasis in gastric cancer is unclear. We examined serum PRSS2 levels in healthy controls and gastric cancer patients by enzyme linked immunosorbent assay (ELISA) and analyzed the correlation between PRSS2 serum level with the clinicopathological characteristics of gastric cancer patients and matrix metalloproteinase-9 (MMP-9) expression. A lentiviral MMP-9 overexpression vector was constructed and used to transfect gastric cancer cells with stable silencing of PRSS2, and migration, invasion and epithelial-mesenchymal transition (EMT) of gastric cancer cells were examined. High serum PRSS2 levels were detected in gastric cancer patients and associated with lymphatic metastasis and TNM stage. Serum PRSS2 was positively correlated with serum MMP-9 level. PRSS2 silencing inhibited EMT, and knock-down of PRSS2 partially abrogated cell metastasis and EMT caused by overexpression of MMP-9. These results suggest that PRSS2 promotes the migration and invasion of gastric cancer cells through EMT induction by MMP-9. Our findings suggest that PRSS2 may be a potential early diagnostic marker and therapeutic target of gastric cancer.

Clinical value of combined serum MMP-2, MMP-9 and TIMP-1 for the prognosis of perianal fistula patients who received minimally invasive surgery.

This study aimed to investigate the clinical value of combined serum matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) for the prognosis of perianal fistula patients. Patients diagnosed and treated for perianal fistula by minimally invasive surgery (MIS) were enrolled. The concentrations of serum MMP-2, MMP-9 and TIMP-1 were measured at 24 h after surgery. Different levels of wound secretion, growth of granulation tissue and wound pain were used as criteria to evaluate surgical incision healing. The receiver operating characteristic curve was used to analyze the predicted assessment value. The concentrations of serum MMP-2 and MMP-9 were significantly higher, while the concentrations of serum TIMP-1 at 24 h after surgery were significantly lower in the poor healing group than in the good healing group. It was further found that high levels of serum MMP-2 and MMP-9 were risk factors for poor healing, while high concentrations of serum TIMP-1 at 24 h after surgery were protective factors for poor healing. High concentrations of serum MMP-2 and MMP-9 and low concentrations of serum TIMP at 24 h after surgery are risk factors for poor healing in perianal fistula patients who receive MIS, and the combined test has a higher predictive value.

A functional MMP-9-1562C>T polymorphism, MMP-9 serum levels and nephrolithiasis risk in a southern Chinese population.

The role of matrix metalloproteinase 9 (MMP-9) in the pathophysiology of chronic kidney disease (CKD), which is associated with a nearly two-fold greater risk for urinary calculi compared to people without CKD, has been demonstrated. The aim of the research is to evaluate the association between MMP-9-1562C>T polymorphism, MMP-9 serum levels and nephrolithiasis risk. A hospital-based case-control study involving 302 kidney stone patients and 408 controls without kidney stone from southern China was conducted. Sanger sequencing was used to genotype the MMP-9-1562C>T polymorphism. The serum MMP-9 was measured in 105 kidney stone patients and 77 controls by enzyme-linked immunosorbent assay. Compared to the control group, the CT genotype was more frequent in nephrolithiasis patients (adjusted OR = 1.60, 95% CI = 1.09-2.37: the risk of developing nephrolithiasis in individuals with CT genotype compared to CC genotype). Moreover, there was also a higher frequency of CT/TT genotypes among patients with nephrolithiasis (adjusted OR = 1.49, 95% CI = 1.02-2.19: the risk of developing nephrolithiasis in individuals with CT/TT genotypes compared to CC genotype). The risk remained for the subgroups of patients aged >53, smokers with pack-years of smoking >20, non-drinkers, non-diabetic patients, patients with hypertension, recurrent episodes and calcium oxalate stones (OR = 2.26, 95% CI = 1.31-3.91; OR = 5.47, 95% CI = 1.10-27.30; OR = 1.76, 95% CI = 1.14-2.72; OR = 1.54, 95% CI = 1.03-2.30; OR = 1.97, 95% CI = 1.01-3.82; OR = 1.67, 95% CI = 1.06-2.62; OR = 1.54, 95% CI = 1.02-2.32, respectively). Biochemical parameters did not differ between genotypes. Compared to controls (18.57 ± 5.80 ng/mL), nephrolithiasis patients had significantly higher serum MMP-9 levels (30.17 ± 6.78 ng/mL, p < 0.001). The serum MMP-9 levels of patients with CT/TT genotypes of MMP-9-1562C>T were significantly higher than those with CC genotype (32.00 ± 6.33 vs. 29.13 ± 6.85 ng/mL, p = 0.037). The MMP-9-1562C>T polymorphism in association with its soluble protein increased the risk of kidney stone, thus suggesting it could be used as a susceptibility biomarker for nephrolithiasis. Further functional studies and larger studies that include environmental exposure data are needed to confirm the findings.

Clinical Significance of MMP7 Levels in Colorectal Cancer Patients Receiving FOLFOX4 Chemotherapy Treatment.

Various studies have shown an association between the anti-cancer drug 5-fluorouracil and matrix metalloproteinase 7 (MMP7). The expression of MMP7 in the serum of colorectal cancer patients, as well as their sensitivity to chemotherapy, were examined using the FOLFOX4 chemotherapy treatment. Serum samples were taken from 216 colorectal cancer patients who had undergone four cycles of gemcitabine and cisplatin treatment. The sera of 216 healthy persons were used as controls. MMP7 levels in the serum were measured by ELISA. Demographic and survival data were collected. MMP7 levels were not associated with sex, age, peritoneal dissemination, liver metastasis, lymph node metastasis, lymphatic invasion, or venous invasion in CRC patients, but were associated with histological grade, tumor size, TNM stage, and depth of tumor invasion. Patients' serum MMP7 expression reduced after treatment. MMP7 expression was significantly lower chemotherapy-sensitive patients compared with chemotherapy-resistant patients. Elevated MMP7 expression was associated with worse prognosis and chemotherapy-sensitive patients had markedly better overall survival compared with chemotherapy-resistant patients. MMP7 expression was potentially associated with the development of colorectal cancer and elevated levels were associated with chemoresistance in CRC patients. Serum MMP7 levels can be used to screen for drug resistance during FOLFOX4 chemotherapy treatment.