Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.35 (matrix metalloproteinase 9)
 2,207 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of childbearing age. The criteria required for the diagnosis identify various phenotypes, with different reproductive, metabolic, and cardiovascular (CV) risk characteristics. Emerging evidence links adipocyte-secreted hormones as candidates in the pathogenesis of endothelial dysfunction in PCOS, independently of additional risk factors. The aim of this review was to collect, analyze, and qualitatively resynthesize evidence on biomarkers of endothelial dysfunction (visfatin, vascular endothelial growth factor [VEGF], matrix metalloproteinase 9 [MMP-9]) in women with PCOS. Women with PCOS exhibit (a) increased plasma visfatin concentrations compared with controls with a similar body mass index; (b) increased VEGF production along with chronic, mild inflammation; and (c) increased MMP-9 concentrations, which might be related to either excessive CV risk or abnormalities of ovarian extracellular matrix remodeling, multiple cyst formation, follicular atresia, and chronic anovulation. As PCOS has been associated with CV risk, early identification of endothelial dysfunction is clinically relevant.
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PMID:Biomarkers of Endothelial Dysfunction in Women With Polycystic Ovary Syndrome. 3096 84

Purpose: To investigate the presence and level of 35 distinct cytokines in the tear fluid obtained from patients with primary acquired nasolacrimal duct obstruction (PANDO) and compare it with controls in an effort to understand the disease etiopathogenesis.Methods: Standard protocols were used for collecting tears from 60 eyes (20 diseased eyes and 20 healthy fellow eyes of unilateral PANDO, 20 control eyes of healthy subjects). A total of 35 analytes involved in inflammation, angiogenesis and wound healing were assessed by multiplex ELISA. Alterations in the tear levels of cytokines in PANDO and their comparison with the levels in the non-diseased fellow eye and healthy volunteers were noted. STRING analysis was used to assess the involved biological pathways of the altered cytokines. Linear mixed effect model was used for statistical analysis. A P value of <0.05 was considered significant.Results: There was significant upregulation of 10 pro-inflammatory cytokines in tears from diseased eyes of PANDO patients in comparison with the non-diseased controls and include matrix metalloproteinase 9 (MMP 9), serpin E1, Interleukin-6 (IL-6), hepatocyte growth factor (HGF), vascular endothelial growth factor-A and R2 (VEGF-A, VEGF R2), platelet-endothelial cell adhesion molecule (PECAM-1), c-reactive protein (CRP), chemokine ligand 2 (CCL2) and platelet-derived growth factor- AA (PDGF-AA). Amongst the anti-inflammatory cytokines, three were significantly upregulated in diseased eyes of PANDO patients in comparison with the non-diseased controls and include granulocyte-colony stimulating factor (G-CSF), retinol binding protein 4 (RBP4) and tissue inhibitor of metalloproteinases -1 (TIMP-1). There were no significant differences between the control eyes of the diseased patient and control eyes of healthy subjects. Based on the significantly altered cytokines, string analysis revealed that the biological pathways involved in the etiopathogenesis of PANDO include inflammation, angiogenesis, negative regulation of apoptosis, cellular proliferation and hormonal regulation.Conclusions: In cases of PANDO, dysregulation of certain cytokines was disease specific. Biological pathways reflect a possible link and interaction between the inflammatory cytokines with vasculature and hormonal microenvironments of the lacrimal drainage system, which in a way is bringing three promising candidates in the PANDO etiopathogenesis on a common ground.
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PMID:Alteration of Tear Cytokine Expressions in Primary Acquired Nasolacrimal Duct Obstruction - Potential Insights into the Etiopathogenesis. 3149 Jul 6

The ability to accurately measure multiple proteins simultaneously in a single assay has the potential to markedly improve the efficiency of clinical tests composed of multiple biomarkers. We investigated the diagnostic accuracy of the two multiplex protein array platforms for detecting a bladder-cancer-associated diagnostic signature in samples from a cohort of 80 subjects (40 with bladder cancer). Banked urine samples collected from Kyoto and Nara Universities were compared to histologically determined bladder cancer. The concentrations of the 10 proteins (A1AT; apolipoprotein E-APOE; angiogenin-ANG; carbonic anhydrase 9-CA9; interleukin 8-IL-8; matrix metalloproteinase 9-MMP-9; matrix metalloproteinase 10-MMP10; plasminogen activator inhibitor 1-PAI-1; syndecan-SDC1; and vascular endothelial growth factor-VEGF) were monitored using two prototype multiplex array platforms and an enzyme-linked immunosorbent assay (ELISA) according to the manufacturer's technical specifications. The range for detecting each biomarker was improved in the multiplex assays, even though the lower limit of quantification (LLOQ) was typically lower in the commercial ELISA kits. The area under the receiver operating characteristics (AUROC) of the prototype multiplex assays was reported to be 0.97 for the multiplex bead-based immunoassay (MBA) and 0.86 for the multiplex electrochemoluminescent assay (MEA). The sensitivities and specificities for MBA were 0.93 and 0.95, respectively, and for MEA were 0.85 and 0.80, respectively. Accuracy, positive predictive values (PPV), and negative predictive values (NPV) for MBA were 0.94, 0.95, and 0.93, respectively, and for MEA were 0.83, 0.81, and 0.84, respectively. Based on these encouraging preliminary data, we believe that a multiplex protein array is a viable platform that can be utilized as an efficient and highly accurate tool to quantitate multiple proteins within biologic specimens.
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PMID:Comparison of Commercial ELISA Kits, a Prototype Multiplex Electrochemoluminescent Assay, and a Multiplex Bead-Based Immunoassay for Detecting a Urine-Based Bladder-Cancer-Associated Diagnostic Signature. 3167 75

We previously revealed the crucial roles of a chemokine, CX3CL1, and its receptor, CX3CR1, in skin wound healing. Although repeated wounds frequently develop into skin cancer, the roles of CX3CL1 in skin carcinogenesis remain elusive. Here, we proved that CX3CL1 protein expression and CX3CR1+ macrophages were observed in human skin cancer tissues. Similarly, we observed the enhancement of CX3CL1 expression and the abundant accumulation of CX3CR1+ tumor-associated macrophages with M2-like phenotypes in the skin carcinogenesis process induced by the combined treatment with 7,12-dimethylbenz[a]anthracene and 12-O-tetradecanoylphorbol-13-acetate. In this mouse skin carcinogenesis process, CX3CR1+ tumor-associated macrophages exhibited M2-like phenotypes with the expression of Wnt3a and angiogenic molecules including VEGF and matrix metalloproteinase 9. Compared with wild-type mice, CX3CR1-deficient mice showed fewer numbers of skin tumors with a lower incidence. Concomitantly, M2-macrophage numbers and neovascularization were reduced with the depressed expression of angiogenic factors and Wnt3a. Thus, the CX3CL1-CX3CR1 axis can crucially contribute to skin carcinogenesis by regulating the accumulation and functions of tumor-associated macrophages. Thus, this axis can be a good target for preventing and/or treating skin cancers.
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PMID:Pivotal Involvement of the CX3CL1-CX3CR1 Axis for the Recruitment of M2 Tumor-Associated Macrophages in Skin Carcinogenesis. 3217 66


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