Serum Levels Of Matrix Metalloproteinase-9 Research Articles

An Exploratory Study Provides Insights into MMP9 and Aβ Levels in the Vitreous and Blood across Different Ages and in a Subset of AMD Patients.

Matrix metalloproteinase-9 (MMP9) and total amyloid-beta (Aβ) are prospective biomarkers of ocular ageing and retinopathy. These were quantified by ELISA in the vitreous and blood from controls (n = 55) and in a subset of age-related macular degeneration (AMD) patients (n = 12) for insights and possible additional links between the ocular and systemic compartments. Vitreous MMP9 levels in control and AMD groups were 932.5 ± 240.9 pg/mL and 813.7 ± 157.6 pg/mL, whilst serum levels were 2228 ± 193 pg/mL and 2386.8 ± 449.4 pg/mL, respectively. Vitreous Aβ in control and AMD groups were 1173.5 ± 117.1 pg/mL and 1275.6 ± 332.9 pg/mL, whilst plasma Aβ were 574.3 ± 104.8 pg/mL and 542.2 ± 139.9 pg/mL, respectively. MMP9 and Aβ showed variable levels across the lifecourse, indicating no correlation to each other or with age nor AMD status, though the smaller AMD cohort was a limiting factor. Aβ and MMP9 levels in the vitreous and blood were unrelated to mean arterial pressure. Smoking, another modifiable risk, showed no association with vitreous Aβ. However, smoking may be linked with vitreous (p = 0.004) and serum (p = 0.005) MMP9 levels in control and AMD groups, though this did not reach our elevated (p = 0.001) significance. A bioinformatics analysis revealed promising MMP9 and APP/Aβ partners for further scrutiny, many of which are already linked with retinopathy.

Association of the matrix metalloproteinases (MMPs) family gene polymorphisms and the risk of coronavirus disease 2019 (COVID-19); implications of contribution for development of neurological symptoms in the COVID-19 patients.

Seemingly, the Matrix metalloproteinases (MMPs) play a role in the etiopathogenesis of coronavirus disease 2019 (COVID-19). Here in this study, we determined the association of MMP9 rs3918242, MMP3 rs3025058, and MMP2 rs243865 polymorphisms with the risk of COVID-19, especially in those with neurological syndrome (NS). We enrolled 500 patients with COVID-19 and 500 healthy individuals. To genotype the target SNPs, the Real-time allelic discrimination technique was used. To determine serum levels of MMPs, Enzyme-linked immunosorbent assay (ELISA) was exerted. The MMP9 gene rs3918242 and MMP3 gene rs3025058 SNP were significantly associated with increased COVID-19 risk and susceptibility to COVID-19 with NS. The serum level of MMP-9 and MMP-3 was significantly higher in COVID-19 cases compared with the healthy controls. Serum MMP-9 and MMP-3 levels were also higher in COVID-19 subjects with NS in comparison to the healthy controls. The polymorphisms in MMP genes were not associated with serum level of MMPs. MMP9 and MMP3 gene polymorphisms increases the susceptibility to COVID-19 as well as COVID-19 with neurologic syndrome, but they probably have no role in the regulation of serum MMP-9 and MMP-3 levels.

Among biomarkers of neutrophil activity, matrix metalloproteinases 8 independently predicts remission of metabolic syndrome

Background and aimsInflammation due to the excess of nutrient intake plays an important role in the pathophysiology of metabolic syndrome (MetS). Here, the potential influence of neutrophils and their degranulation markers on MetS improvement upon dietary and behavioral counselling, has been investigated. Specifically, we aimed at investigating their role as potential predictors of metabolic syndrome improvements. Methods and Resultspatients with MetS (n = 127) received behavioral and dietary recommendations before follow-up at 6 months. Serum levels of matrix metalloproteinases (MMP)8, MMP9, myeloperoxidase (MPO), tissue inhibitor of MMP (TIMP)-1, TIMP-2, TIMP-3 and resistin were tested at baseline. In the whole cohort, baseline levels of proinflammatory MMP8, MMP9 and MPO increased together with the number of MetS criteria. Seventy-three (57%) patients experienced a reduction in MetS-defining criteria at follow-up. With respect to those with no improvement, such individuals showed lower weight and waist circumference at enrolment, less frequent smoking habits, higher levels of triglycerides and lower circulating MMP8. At logistic regression analysis, baseline MMP8 showed negative predictive ability (odds ratio (OR) 0.979 [0.961–0.997]; p = 0.025) against MetS improvement. Such findings hold true even when included in the backward stepwise logistic regression model confirming MMP8 as an independent predictor (OR 0.970 [0.949–0.993]; p = 0.009). Receiver operating characteristic (ROC) curve confirmed the predictive ability of MMP8 combined in a model including baseline MetS criteria and waist circumference. Bootstrap resampling analysis internally validated our findings. ConclusionImprovement of MetS is independently associated with baseline low MMP-8 levels, suggesting a pivotal role for inflammation in metabolic alteration.

Serum MMP-9, SP-D, and VEGF levels reflect the severity of connective tissue disease-associated interstitial lung diseases

BackgroundInterstitial lung disease (ILD) is a common pulmonary complication of connective tissue disease (CTD). This study aims to evaluate the clinical diagnostic value of matrix metalloproteinase-9 (MMP-9), surfactant protein-D (SP-D), and vascular endothelial growth factor (VEGF) as potential biomarkers for CTD-ILD.MethodsThis research included 33 CTD-ILD patients, 31 CTD patients without ILD, and 24 healthy control subjects. Then, the value of biomarkers for the diagnosis and evaluation of CTD-ILD was assessed through high-resolution computed tomography (HRCT) findings and pulmonary function test (PFT) parameters.ResultsThe serum MMP-9, SP-D, and VEGF levels in the CTD-ILD group were higher than those in the CTD-NILD group and healthy group. The ROC curve indicates that VEGF has good to excellent diagnostic performance in diagnosing CTD-ILD, the cut-off that best optimizes sensitivity and specificity in diagnosing CTD-ILD is 277.60 pg/ml (sensitivity, 87.9%; specificity, 83.6%), with an area under the curve (AUC) of 0.905 (95% confidence interval (CI) 0.842–0.968); The ROC curve for MMP-9 suggests this biomarker is fair for diagnosis of CTD-ILD(sensitivity, 81.8%; specificity, 81.8%), with an AUC of 0.867 (95% CI 0.784–0.950), but SP-D only provided lower specificity with higher sensitivity in diagnosing CTD-ILD(sensitivity, 90.9%; specificity, 40.0%). The different serum biomarkers are more specific and sensitive when combined to diagnose ILD. The semiquantitative score for the degree of ILD severity on HRCT was positively correlated with SP-D and VEGF levels (r = 0.461, P = 0.007; r = 0.362, P = 0.039), and serum MMP-9 levels were elevated in the UIP subgroup compared to the non-UIP subgroup. The percentage of diffusing capacity of the lung for carbon monoxide (DLco) (% predicted) had a negative correlation with the SP-D level (r = − 0.407, P = 0.044) and a statistically negative correlation between MMP-9 and the forced vital capacity (FVC) (r = − 0.451, P = 0.024).ConclusionsSerum MMP-9, SP-D, and VEGF levels may have clinical value in screening and evaluating the severity of CTD-ILD.

Detection of interstitial pneumonia with autoimmune features and idiopathic pulmonary fibrosis are enhanced by involvement of matrix metalloproteinases levels and clinical diagnosis.

Higher detection of interstitial pneumonia with autoimmune features (IPAF), and idiopathic pulmonary fibrosis (IPF), has significant diagnostic and therapeutic implications. Some matrix metalloproteinases (MMPs) have become reliable diagnostic biomarkers in IPAF and IPF in previous studies, yet relevant reliability remains to be recognized. In this study, 36 ILDs patients, including 31 IPAF patients (Mean ± SD, 50.20 ± 5.10 years; 16 [51.6%] females) and five IPF patients (Mean ± SD, 61.20 ± 6.73 years; one [20.0%] females) were retrospectively enrolled. Serial serum samples were collected from patients with IPAF and IPF between January 2019 and December 2020. Notably, Serum MMPs levels were measured by U-PLEX Biomarker Group 1(Human) Multiplex Assays (MSD, USA). A combination of MMPs and combinatorial biomarkers was strongly associated with clinical subjects in this study (AUC, 0.597 for Stability vs. Improvement and 0.756 for Stability vs. Exacerbation). Importantly, the AUC of MMP-12 reaches 0.730 (p < 0.05, Stability AUC vs. Improvement AUC) while MMP-13 reaches 0.741 (p < 0.05, Stability AUC vs. Exacerbation AUC) showed better performance than other MMPs in two comparisons. Clinical risk factors and MMPs are strongly associated with either stratification of the disease of progression of IPAF or in two IPAF and IPF independent cohorts. To our knowledge, this is the first to illustrate that MMP-12 and MMP-13 may be expected to become typical promising biomarkers in Improvement - IPAF and Exacerbation - IPAF, respectively.

Activation of STAT3 (signal transducer and activator of transcription 3) in synovial tissues from the hip joint in the early stage of rapidly destructive coxopathy.

Interleukin-6 signaling activates signal transducer and activator of transcription 3 (STAT3), resulting in matrix metalloproteinase-3 (MMP-3) production. The hip joints with rapidly destructive coxopathy (RDC) show rapid chondrolysis, probably by increased MMP-3. This study aimed to elucidate STAT3 activation in the synovial tissues with joint destruction in the early stage of RDC. Synovial tissues within 7 months from the disease onset were obtained from four RDC patients with femoral head destruction and high serum levels of MMP-3. RDC synovial tissues demonstrated the synovial lining hyperplasia with an increase of CD68-positive macrophages and CD3-positive T lymphocytes. STAT3 activation was found in the synovial tissues by immunohistochemistry using anti-phospho-STAT3 antibody. The majority of phospho-STAT3-positive cells were the synovial lining cells and exhibited negative expression of the macrophage or T cell marker. Treatment with CP690,550, a Janus Kinase inhibitor, resulted in a decrease in phospho-STAT3-positive cells, especially with high intensity, indicating effective suppression of STAT3 activation in RDC synovial tissues. Inhibitory effect of CP690,550 could work through the Janus Kinase/STAT3 axis in the synovial tissues in the early stage of RDC. Thus, STAT3 may be a potential therapeutic target for prevention of joint structural damage in RDC.

Relationship between MMP-9 serum levels and tHcy levels and total imaging load and cognitive dysfunction

ObjectivesTo investigate the correlation and predictive value of serum matrix metalloproteinase-9 (MMP-9) level with cognitive dysfunction and total imaging load in patients with cerebral small vessel disease (CSVD). MethodsA total of 80 patients with CSVD who were admitted to the First Affiliated Hospital of Xinxiang Medical University between April 2019 and April 2020 were enrolled. All subjects underwent T1-weighted imaging (T1WI), T2WI, fluid-attenuated inversion recovery (FLAIR), diffusion weighted imaging (DWI), serum sample collection, and assessment of cognitive function at a specific time-point after admission. According to the results of the neuropsychological test, subjects were divided into cognitive dysfunction group (n=40) and normal cognitive function group (n=40). The total imaging load was estimated according to the neuroimaging findings. Serum MMP-9 level was measured by an enzyme-linked immunosorbent assay (ELISA) kit. Beside, serum MMP-9 level and total imaging load were compared between the two groups. ResultsSerum levels of MMP-9 and plasma total homocysteine (tHcy) were negatively correlated with cognitive function (P<0.05). Serum MMP-9 level was found as a significant factor for diagnosing cognitive impairment due to CSVD (area under the curve (AUC), 0.756; sensitivity and specificity were 97.5% and 75.0%, respectively). THcy level was also found as significant factor for diagnosing cognitive impairment due to CSVD (area under the curve (AUC), 0.727; sensitivity and specificity were 97.5% and 75.0%, respectively). ConclusionSerum MMP-9 level and tHcy level were significantly correlated with cognitive function in patients with CSVD. Serum MMP-9 level has a specific correlation with the total imaging load in patients with CSVD. It plays an important role in diagnosing cognitive impairment in patients with CSVD.

Association Between Serum Matrix Metalloproteinase-2 Levels and Mean Doppler Pulsatility Index of Uterine Arteries in Patients with Preeclampsia

Abstract Background: Мatrix metalloproteinase-2 (MMP-2) is an enzye from the gelatinases family involved mainly in collagen degradation. It is also known as a key regulator of normal vascular remodelling during a healthy pregnancy. Failure of regulation of MMP-2 has been associated with abnormal vasodilation, placentation, uterine expansion and development of preeclampsia (PE). Aims: (1) determine serum MMP-2 levels in women with PE and healthy pregnancy, (2) evaluate mean uterine arteries Doppler pulsatility index (UtA PI) and (3) investigate the a possible association between these parameters. Materials and methods: This was a case-control study. Fifty-five women with PE (mean age 24.9 ± 6 years) and a control group of 35 women with normal pregnancies (mean age 24.7 ± 5.4 years) were examined. An enzyme-linked immunosorbent assay (ELISA) was used to determine serum levels of MMP-2. Mean UtA PI were evaluated by Doppler velocimetry. Results: Serum ММР-2 levels in preeclampsia were significantly higher than in women with normal pregnancy 11.7 (9.1÷15.5) vs. 7.7 ng/ml (6.5÷13.4) (p = 0.016). Mean UtA PI was significantly higher in preeclampsia than in healthy pregnant women: 1.12 (0.82÷1.5) vs. 0.75 (0.69÷0.85); (p = 0.024). ММР-2 correlated with UtA PI (r = 0.214; p = 0.043). Cutoff value at 14 ng/ml for MMP-2 was found to discriminate between PE and healthy pregnancy. Conclusion: Our data showed an association between serum MMP-2 and Mean UtA PI. We suggest that MMP-2 could have a potential imply on maternal uterine arteries’ structure, favoring their constriction, increased resistance and abnormal uterine vascular remodeling. Further studies are warranted to clarify whether determination of MMP-2 cutoff value might contribute in the diagnosic work-out strategy for PE.

Study on the Relationship between MMP-2, MMP-9 Gene Polymorphisms, and the Risk of Colorectal Cancer.

Objective The aim of the study is to explore the relationship between matrix metalloproteinase 2 (MMP-2) and matrix metalloproteinase 9 (MMP-9) gene polymorphisms and the risk of colorectal cancer. Methods From January 2019 to December 2021, 308 patients with colorectal cancer in our hospital were selected to be included in the colorectal cancer group and 300 normal healthy people were included in the control group. We perform genotyping, compare the genotype frequencies between the colorectal cancer group and the control group, calculate the relationship between MMP-2 and MMP-9 gene polymorphisms and disease risk, and analyze the genotype distribution characteristics of colorectal cancer patients with different pathological stages and lymph node metastasis status. The expression levels of serum MMP-2 and MMP-9 in patients with different genotypes were compared. Results The frequency of CC genotype and C gene at the MMP-2 gene−735 (C/T) locus in the colorectal cancer group was higher than that of the control group, and the frequency of TT genotype and T gene at MMP-9 gene−1562 (C/T) locus was a higher control group (P < 0.05). The comparison of genotype and gene frequency distribution of MMP-2 gene−1306 (C/T), −790 (T/G), and MMP-9 gene R668Q and P574R between the colorectal cancer group and the control group (P > 0.05); MMP-2 gene−735 (C/T) locus CC genotype and MMP-9 gene−1562 (C/T) locus TT genotype are dangerous genotypes for colorectal cancer. OR values were 1.490 (95% CI: 1.085–2.047), 1.519 (95% CI: 1.061–2.174); TNM stage III-IV, the proportion of CC genotype and TT genotype at MMP-9 gene−1562 (C/T) locus in patients with lymph node metastasis is higher than that without lymph node metastasis of TNM stage I-II patients (P < 0.05); MMP-2 gene in colorectal cancer patients. Serum MMP-2 levels in patients with CC genotype at 735 (C/T) locus were higher than those with CT + TT genotype, and serum MMP-9 levels in patients with TT genotype at MMP-9 gene−1562 (C/T) locus were higher CT + CC genotype patients (P < 0.05). Conclusion The CC genotype at −735 (C/T) locus of the MMP-2 gene and the TT genotype at−1562 (C/T) locus of the MMP-9 gene are risk genotypes for the development of colorectal cancer.

Assessment of Some Platelet Activating Markers and Secretory Status with Clinical Manifestations in Multiple Sclerosis Iraqi Patients

Patients with Multiple sclerosis (MS) are presented with different degree of disability based on Expanded disability status scale (EDSS). Several studies reported that ABH non-secretors have higher prevalence in different auto-immune diseases, also platelets have a multi-form participation in development of MS. Therefore, this study aimed to assess the correlation of clinical manifestations in patients with platelet-activating factor (PAF), P-Selectin, matrix metalloproteinase-9 (MMP-9) and ABH secretor status. Fifty Iraqi patients with relapsing-remitting multiple sclerosis (RRMS) were enrolled and divided into two subgroups; 36 of them with no disability (D0), their EDSS score ranging between 0-1.5, and the rest 14 patients with different degrees of disability (D+), their EDSS score ≥ 2. Along with patients, 20 healthy subjects were involved to act as a control group. Results showed significant elevation of PAF, P-Selectin, and MMP-9 levels in patients compared with those in the control group. However, only PAF level in D+ patients is significantly higher than D0 and positively correlated with duration of disease and serum level of MMP-9. Moreover, the frequency of non-secretors among RRMS patients is significantly higher than those in the control group and have a higher level of MMP-9, so may act as a risk factor for getting MS disease via increasing the serum level of MMP-9.

Is Matrix Metalloproteinase-9 Associated with Post-Stroke Cognitive Impairment or Dementia?

Matrix metalloproteinase-9 (MMP-9) is a significant protease required for synaptic plasticity, learning, and memory. Yet, the role of MMP-9 in the occurrence and development of cognitive decline after ischemic stroke is not fully understood. In this study, we used clinical data experiments to further investigate whether MMP-9 and genetic polymorphism are associated with post-stroke cognitive impairment or dementia (PSCID). A total of 148 patients with PSCID confirmed by the Montreal Cognitive Assessment (MoCA) 3 months after onset (PSCID group) were included in the study. The MMP-9 rs3918242 polymorphisms were analyzed using polymerase chain reaction coupled with restriction fragment length polymorphism, and the serum level of MMP-9 was measured using enzyme-linked immunosorbent assay (ELISA). The same manipulations have been done on 169 ischemic stroke patients without cognitive impairment (NCI group) and 150 normal controls (NC group). The expression level of serum MMP-9 in the PSCID group and NCI group was higher compared to the NC group, and the levels in the PSCID group were higher than that in the NCI group (all p < 0.05). Diabetes mellitus, hyperhomocysteinemia, and increased serum MMP-9 levels were the main risk factors of cognitive impairment after ischemic stroke. The serum level of MMP-9 was negatively correlated with the MoCA score, including visual-spatial executive, naming, attention, language, and delayed recall. Genetic polymorphism showed that TC genotype with MMP-9 rs3918242 and CC genotype were associated with a significantly increased risk of PSCID; moreover, the TC genotype significantly increased the risk of cognitive impairment. In the TCCC genotype of MMP-9 rs3918242, diabetes mellitus and hyperhomocysteinemia were associated with the increased risk of PSCID; also, hyperhomocysteinemia could increase the risk of cognitive impairment. MMP-9 level and MMP-9 rs3918242 polymorphism have an important role in the occurrence and development of post-stroke cognitive impairment or dementia (PSCID).

Anti-arthritic effects of Schisandra chinensis extract in monosodium iodoacetate-induced osteoarthritis rats.

The present study aimed to investigate the therapeutic effects of Schisandra chinensis (SC) extract on clinical symptoms of osteoarthritis and the modulating effect on the mechanisms associated with the progression of osteoarthritis in a rat model of monosodium iodoacetate (MIA)-induced osteoarthritis. Osteoarthritis-induced rats were randomized into four groups: MIA injection control (MC), MIA injection with celecoxib (PC), MIA injection with SC extract 100mg/kg (SC100), and MIA injection with SC extract 200mg/kg (SC200). Another healthy group received a saline injection as a negative control (NC). During the treatment, weight-bearing measurements were performed once a week for 4 weeks. Histopathological and biochemical analyses of the joints, blood, and chondrocyte tissue were performed following the completion of treatment. Compared with MC rats, SC rats demonstrated significantly alleviated pain behavior, bone erosion, and cartilage degradation. SC reduced serum levels of matrix metalloproteinases and pro-inflammatory cytokines. SC treatment also reversed the levels of biomarkers such as Collagen II and ADAMTS4 in the cartilage tissue. Moreover, SC administration inhibited the phosphorylation levels of nuclear factor kappa B (NF-κB) and NF-κB Inhibitor alpha. This study demonstrates that SC ameliorated osteoarthritis at in vivo level. Our results suggest that SC might be a potential therapeutic agent for osteoarthritis.

Therapeutic Effects of the Proximal Femoral Nail for the Treatment of Unstable Intertrochanteric Fractures.

Objective The aim of this study was to analyze the clinical effect of the proximal femoral nail on elderly patients with unstable intertrochanteric fracture and the effect of the proximal femoral nail on serum levels of matrix metalloproteinases (MMPs) and osteoprotegerin (OPG). Methods The elderly patients with unstable intertrochanteric fracture of the femur admitted to our hospital from January 2017 to January 2021 were studied. 100 patients were randomly divided into two groups: the control group (n = 50) and the observation group (n = 50). The patients in the control group were treated with a proximal femoral locking compression plate. The patients in the observation group were treated with the proximal femoral antirotation intramedullary nail. The clinical therapeutic effects of the two groups and the changes in serum MMPs and OPG levels before and after treatment were analyzed. Results Compared with the control group, the operation time, postoperative landing time, and fracture healing time of the observation group were significantly shortened, and intraoperative blood loss was significantly reduced (P < 0.05). Compared with the control group, the total effective rate of patients in the observation group was significantly higher (P < 0.05). After treatment, the levels of CRP, IL1β, IL2, MMP-2, MMP-6, TIMP-1, and RANKL decreased significantly in both groups (P < 0.05), while the levels of OPG increased significantly (P < 0.05). Compared with the control group, the changes in the above indexes were more obvious in the observation group (P < 0.05). Conclusion The proximal femoral antirotation intramedullary nail has a better therapeutic effect on elderly patients with unstable intertrochanteric fracture, and the level of MMPs and OPG may be related to the treatment process.

Prenatal exposure to nickel and atopic dermatitis at age 3 years: a birth cohort study with cytokine profiles.

Nickel, the fifth most common element on Earth, is the leading inducer of contact allergies in humans, with potent immunological effects. Nickel-induced contact allergies predominantly affect females. Maternal exposure to nickel has been associated with several developmental abnormalities. However, how a maternal nickel exposure affects the development of atopic diathesis and immune abnormalities in children has never been addressed. We aimed to determine whether maternal nickel exposure affects the development of atopic dermatitis and immune abnormalities in their children. Using a birth cohort study, we analysed 140 mother-child pairs recruited in 2012-2015 from central Taiwan. Maternal exposure to nickel was estimated using urinary nickel levels measured by inductively coupled plasma mass spectrometry (ICP-MS). The serum levels of 65 analytes and IgE in 3-year-old children were profiled with a multiplex ELISA. The correlation between the maternal urinary nickel concentration and serum analyte levels was assessed using Spearmen's correlation. Multivariant regression analysis was performed to evaluate the association between maternal urinary nickel levels and serum analyte concentrations in their children. The geometric means of the maternal urinary nickel and the children's serum IgE levels were 2.27 μg/L and 69.71 IU/mL, respectively. The maternal nickel exposure was associated with increased serum levels of IL-1β, IL-2, TNF-α, and leukaemia inhibitory factor (LIF) but with decreased serum levels of matrix metalloproteinase-1 (MMP-1), IL-2R, and eotaxin-1 in the children. In addition, the development of childhood atopic dermatitis at 3 years old was significantly associated with the child's serum levels of IgE and IL-2R, but it was negatively associated with the maternal nickel exposure. This is the first study showing the potential immunological effects of maternal nickel exposure in their children at an early developmental stage.

The Significance of FDG PET/CT-Derived Parameters in Determining Prognosis of Cases with Pancreatic Adenocarcinoma: A Prospective Study.

Background and objectives: Pancreatic adenocarcinoma represents one of the common malignancies with a relatively poor prognosis. However, early detection of this type of cancer may prove to be curable. Recent advancements in the radiological techniques might represent a hope for the early diagnosis and prediction of prognosis of pancreatic adenocarcinoma. This study aimed to assess the prognostic value of the primary tumor volumetric parameters obtained from FDG PET/CT first stage for the overall survival (OS) and progression-free survival (PFS) of patients with pancreatic adenocarcinoma and to explore the possible correlation between serum matrix metalloproteinase-2 (MMP-2) and the patients’ characteristics. Methods: Fifty patients with pancreatic adenocarcinoma were subjected to FDG PET/CT scan. The SUVpeak, SUVmax, and the metabolic tumor volume (MTV) were determined, as well as the SUVmean of the liver. Moreover, serum levels of MMP-2 were assessed. Follow-up of the patients was carried out for sixty months with determination of PFS and OS. Results: Peak SUV ≥ 3.9 was significantly correlated with the primary pancreatic lesions’ mean total glycolytic activity of >92 g, and MTV and was directly correlated with mortality. There was a positive correlation between peak SUV ≥ 3.9 and 50% SUVmax threshold > 82. Moreover, there was significant correlation between the total glycolytic activity and the studied clinicopathologic factors, except the age and sex of the patients and ECOG performance status. In addition, FDG uptake and the tumor glycolytic activity were substantially linked with a shorter PFS. Similarly, a strong correlation was found between MTV and PFS. Serum MMP-2 levels showed a significant relationship with the performance status, tumor stage, SUVmax threshold, and the glycolytic activity. Conclusions: Peak SUV, main lesion SUVmax, serum MMP-2, and the tumor glycolytic activity are good predictors of PFS of patients with pancreatic adenocarcinoma.

Elevated IgG and IgM Autoantibodies to Advanced Glycation End Products of Vascular Elastin in Hypertensive Patients with Type 2 Diabetes: Relevance to Disease Initiation and Progression.

The increased glycation of elastin is an important factor in vascular changes in diabetes. Using the ELISA method, we determined serum levels of IgM and IgG autoantibodies to advanced glycation end products of vascular elastin (anti-AGE EL IgM and anti-AGE EL IgG) in 59 hypertensive patients with type 2 diabetes (T2D) and 20 healthy controls. Serum levels of matrix metalloproteinases-2 and -9 (MMP-2 and MMP-9) and the C-reactive protein (CRP) were also determined. The levels of anti-AGE EL IgM antibodies in the T2D group were similar to those in the control group, while those of anti-AGE EL IgG antibodies were significantly higher (p = 0.017). Significant positive correlations were found between the levels of anti-AGE EL IgM antibodies and MMP-2 (r = 0.322; p = 0.013) and between the levels of anti-AGE EL IgG antibodies and CRP (r = 0.265; p = 0.042). Our study showed that elevated anti-AGE EL IgG antibody levels may be an indicator of the enhanced AGE-modification and inflammatory-mediated destruction of vascular elastin in hypertensive patients with T2D. Anti-AGE EL IgM antibodies may reflect changes in vascular MMP-2 activity, and their elevated levels may be a sign of early vascular damage.

The effect of atorvastatin on the blood-brain barrier biomarkers in acute intracerebral hemorrhage, a pilot clinical trial

ObjectivePrior studies have shown statins provide neuroprotection by targeting secondary brain injury pathways and regulating cytokine production. We aimed to evaluate the association between statin administration and molecular outcomes in acute Intracranial hemorrhages (ICHs). MethodsAdult patients with acute spontaneous ICH were recruited and randomly allocated into two groups: group A received atorvastatin (40 mg/day) orally in addition to routine antihypertensive medications, while group B only received routine antihypertensives. Serum levels of matrix metalloproteinase-9 (MMP-9), and vascular endothelial growth factor (VEGF), as primary outcomes, were measured at baseline, and after 45 days. ResultsThirty-nine ICH patients (group A: 20; group B: 19) were analyzed. A notable elevation in VEGF and a reduction in MMP-9 levels were detected in group A compared to those in group B (P-value = 0.024 and 0.008, respectively). ConclusionOur data suggest that atorvastatin in the acute phase of ICH could improve the serum levels of neuroprotective molecular biomarkers.

Serum levels of matrix metalloproteinases as prognostic markers for severe dengue with plasma leakage

BackgroundPlasma leakage is a major pathogenic manifestation of severe dengue and is a precursor of life-threatening complications associated with dengue. Accumulating evidence indicates the role of Matrix Metalloproteinases (MMPs) in mediating vascular permeability and plasma leakage following induction by the dengue virus. This study aims to investigate the utility of MMP-2, MMP-3, and MMP-9 in predicting the severity of dengue infection and further explore the relationship of these markers with the pathogenic factors associated with plasma leakage. MethodsThe dengue-positive subjects were classified into mild and severe dengue groups based on the manifestation of warning signs. The samples in each group and healthy controls were quantified for basic laboratory characteristics. The levels of MMP-2, MMP-3, MMP-9, and Macrophage migration inhibitory factor (MIF) were estimated in all serum samples using a multiplex bead-based assay. ResultsMMP-2 and MMP-9 were markedly elevated in severe dengue patients compared to mild dengue patients and healthy controls. No alteration in the circulating levels of MMP-3 was observed between the study groups. ROC curve analysis indicated that MMP-2 and MMP-9 exhibited good potential for predicting severe dengue. Notably, an increase in MMP-9 was associated with increased MIF and Hematocrit levels in severe dengue patients. ConclusionMMP-2 and MMP-9 could serve as prognostic biomarkers for severe dengue. These findings also identify the association of MMP-9 with markers of plasma leakage, thereby encouraging further studies to explore the therapeutic potential of targeting MMP-9 in managing plasma leakage in severe dengue.

TNF-α Inhibitors in Combination with MTX Reduce Circulating Levels of Heparan Sulfate/Heparin and Endothelial Dysfunction Biomarkers (sVCAM-1, MCP-1, MMP-9 and ADMA) in Women with Rheumatoid Arthritis.

Sulfated glycosaminoglycans (sGAGs) are likely to play an important role in the development and progression of rheumatoid arthritis (RA)-associated atherosclerosis. The present study investigated the effect of anti-tumor necrosis factor-α (anti-TNF-α) therapy in combination with methotrexate on plasma sGAG levels and serum markers of endothelial dysfunction. Among sGAG types, plasma chondroitin/dermatan sulfate (CS/DS) and heparan sulfate/heparin (HS/H) were characterized using electrophoretic fractionation. Serum levels of soluble vascular cell adhesion molecule-1 (sVCAM-1), monocyte chemoattractant protein-1 (MCP-1), matrix metalloproteinase-9 (MMP-9) and asymmetric dimethylarginine (ADMA) were measured by immunoassays. The measurements were carried out four times: at baseline and after 3, 9 and 15 months of anti-TNF-α therapy. All analyzed parameters, excluding ADMA, were significantly elevated in patients with RA before the implementation of biological therapy compared to healthy subjects. Performed anti-TNF-α treatment led to a successive decrease in HS/H levels toward normal values, without any effect on CS/DS levels in female RA patients. The treatment was also effective at lowering the serum levels of sVCAM-1, MCP-1, MMP-9 and ADMA. Moreover, a significant positive correlation was found between the circulating HS/H and the 28 joint disease activity score based on the erythrocyte sedimentation rate (DAS28-ESR, r = 0.408; p <0.05), MCP-1 (r = 0.398; p <0.05) and ADMA (r = 0.396; p <0.05) in patients before the first dose of TNF-α inhibitor. In conclusion, a beneficial effect of anti-TNF-α therapy on cell-surface heparan sulfate proteoglycans (HSPGs)/HS turnover and endothelial dysfunction was observed in this study. This was manifested by a decrease in blood HS/H levels and markers of endothelial activation, respectively. Moreover, the decrease in the concentration of HS/H in the blood of patients during treatment, progressing with the decline in disease activity, indicates that the plasma HS/H profile may be useful for monitoring the efficacy of anti-TNF-α treatment in patients with RA.

Angiogenic activities of interleukin-8, vascular endothelial growth factor and matrix metalloproteinase-9 in breast cancer

Angiogenesis is a major contributor to tumor growth and metastasis within breast cancer tumor microenvironment in which different proangiogenic factors have been identified and associated with tumor progression, metastasis and poor prognosis. The aim of the current study was to evaluate the angiogenesis among breast cancer patients through ex vivo assessment of the angiogenic factors interleukin 8 (IL-8) and vascular endothelial growth factor (VEGF)-A expressions in excised tumor tissues as well as matrix metalloproteinase 9 (MMP-9) serum levels as well as the prognostic value of MMP-9. Our study included 28 invasive ductal carcinoma female patients who were scheduled for modified radical mastectomy at Medical Research Institute, Alexandria University, Egypt and 10 control subjects. Both IL-8 and VEGF-A expressions were immunohistochemically detected in tumor tissues and serum MMP-9 was determined by ELISA. Although no significant correlations were found between each of IL-8, VEGF-A, MMP-9 levels, and patients' clinicopathological parameters, a significant positive correlation was found between these angiogenic factors each other suggesting their synergistic roles in proceeding angiogenesis. Higher serum MMP-9 level was detected in breast cancer patients compared to the control group, indicating that it can be used as a prognostic biomarker in breast cancer patients.