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Carlos Fernandez-Patron, Zamaneh Kassiri, Dickson Leung
Matrix metalloproteinase-2 (MMP-2) is a 72-kDa zinc- and calcium-dependent endopeptidase with intracellular and extracellular functions ranging from the modulation of extracellular matrix remodeling to cell growth and migration, angiogenesis, inflammation, and metabolism. An upregulation of MMP-2 activity has the potential to deregulate lipid metabolism through the cleavage of numerous metabolic mediators including plasma lipoproteins and cell surface receptors of lipoproteins. Paradoxically, MMP-2 deficiency induces inflammation and deregulates metabolism...
September 15, 2016: Comprehensive Physiology
W Michael Dismuke, Mikael Klingeborn, W Daniel Stamer
Exosomes are emerging as important mediators of cell-matrix interactions by means of specific adhesion proteins. Changes in the tissue-specific exosomal protein expression may underlie pathological conditions whereby extracellular matrix turnover and homeostasis is disrupted. Ocular hypertension due to extracellular matrix accumulation in the trabecular meshwork is a hallmark of glucocorticoid-induced glaucoma. In the trabecular meshwork, exosomal fibronectin mediates cell matrix interactions at cellular structures called "invadosomes"...
2016: PloS One
I B Beloglazova, E S Zubkova, Z I Tsokolaeva, Yu S Stafeev, K V Dergilev, E I Ratner, M V Shestakova, O Yu Sukhareva, E V Parfenova, M Yu Men'shikov
We studied the effect of urokinase, its recombinant forms, and domain fragments on migration and proliferation of adipose tissue mesenchymal stromal cells (MSCs) and MMP secretion by these cells. Urokinase, but not its recombinant forms, slightly induced directed migration of MSCs. Spontaneous migration of MSCs increased under the action of urokinase or its isolated kringle domain. Migration induced by platelet-derived growth factor was inhibited by proteolytically inactive form of urokinase, the kringle domain, and blocking antibody to urokinase receptor...
October 26, 2016: Bulletin of Experimental Biology and Medicine
Takuya Hirai, Keigo Ikeda, Maki Fujishiro, Hiroshi Tsushima, Kunihiro Hayakawa, Satoshi Suzuki, Ayako Yamaguchi, Kazuhisa Nozawa, Shinji Morimoto, Yoshinari Takasaki, Hideoki Ogawa, Kenji Takamori, Naoto Tamura, Iwao Sekigawa
The study aims to confirm the feasibility of new oral triple combination therapy using methotrexate (MTX), mizoribine (MZR), and tacrolimus (TAC) in patients with rheumatoid arthritis (RA) by in vitro and clinical analyses. Triple therapy with a combination of MTX, MZR, and TAC was used for an in vitro study with osteoclasts and a prospective clinical study in order to show the efficacy of these agents against refractory RA. In particular, low-dose TAC or MZR was added to treat 14 patients with RA that was resistant to MTX + MZR or MTX + TAC dual therapy...
October 25, 2016: Clinical Rheumatology
Klaus Häfelein, Andrea Preuße-Prange, Peter Behrendt, Bodo Kurz
Meniscal integrity is a prerequisite for sustained knee joint health and prevention of meniscal degeneration is a main research goal. Cartilage-protective effects of selenium have been described, but little is known about the impact on the meniscus. We therefore investigated the influence of sodium selenite on meniscal explants under tumor necrosis factor-alpha (TNFα)-stimulated proinflammatory conditions. Meniscal explant disks (3 mm diameter × 1 mm thickness) were isolated from 2-year-old cattle and incubated with TNFα (10 ng/ml) and sodium selenite (low dose, LoD 6...
October 25, 2016: Biological Trace Element Research
Lauren Tracy Daly, David M Tsai, Mansher Singh, Kristo Nuutila, Raquel A Minasian, Cameron C Y Lee, Elizabeth Kiwanuka, Florian Hackl, Andrew B Onderdonk, Johan P E Junker, Elof Eriksson, Edward J Caterson
BACKGROUND: Wound infection can impair postoperative healing. Topical antibiotics have potential to treat wound infection and inflammation and minimize the adverse effects associated with systemic antibiotics. METHODS: Full-thickness porcine wounds were infected with Staphylococcus aureus. Using polyurethane wound enclosure devices, wounds were treated with topical 100 μg/ml minocycline, topical 1000 μg/ml minocycline, topical saline control, or 4 mg/kg intravenous minocycline...
November 2016: Plastic and Reconstructive Surgery
J-J Liu, Y Lu, N-N Ping, X Li, Y-X Lin, C F Li
Oxidative stress plays an important role in pressure overload-induced cardiac remodeling. The purpose of this study was to determine whether apocynin, a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor, attenuates pressure overload-induced cardiac remodeling in rats. After abdominal aorta constriction, the surviving rats were randomly divided into four groups: sham group, abdominal aorta constriction group, apocynin group, captopril group. Left ventricular pathological changes were studied using Masson's trichrome staining...
October 26, 2016: Physiological Research
Ximin Zhu, Yongliang Cao, Lixiang Wei, Ping Cai, Haochen Xu, Haiyu Luo, Xiaofei Bai, Lu Lu, Jian-Ren Liu, Wenying Fan, Bing-Qiao Zhao
Spontaneous intracerebral haemorrhage (ICH) is the most devastating stroke subtype and has no proven treatment. von Willebrand factor (VWF) has recently been demonstrated to promote inflammation processes. The present study investigated the pathophysiological role of VWF after experimental ICH. Functional outcomes, brain edema, blood-brain barrier (BBB) permeability, cerebral inflammation and levels of intercellular adhesion molecule-1 (ICAM-1) and matrix metalloproteinase-9 (MMP-9) were measured in a mouse model of ICH induced by autologous blood injection...
October 26, 2016: Scientific Reports
Alessandra Ammazzalorso, Barbara De Filippis, Cristina Campestre, Antonio Laghezza, Alessandro Marrone, Rosa Amoroso, Paolo Tortorella, Mariangela Agamennone
Matrix metalloproteinases (MMPs) are an important family of zinc-containing enzymes with a central role in many physiological and pathological processes. Although several MMP inhibitors have been synthesized over the years, none reached the market because of off-target effects, due to the presence of a zinc binding group in the inhibitor structure. To overcome this problem non-zinc-binding inhibitors (NZIs) have been recently designed. In a previous article, a virtual screening campaign identified some hydroxynaphtyridine and hydroxyquinoline as MMP-2 non-zinc-binding inhibitors...
October 22, 2016: International Journal of Molecular Sciences
José María Gutiérrez, Teresa Escalante, Alexandra Rucavado, Cristina Herrera, Jay W Fox
Snake venom metalloproteinases (SVMPs) affect the extracellular matrix (ECM) in multiple and complex ways. Previously, the combination of various methodological platforms, including electron microscopy, histochemistry, immunohistochemistry, and Western blot, has allowed a partial understanding of such complex pathology. In recent years, the proteomics analysis of exudates collected in the vicinity of tissues affected by SVMPs has provided novel and exciting information on SVMP-induced ECM alterations. The presence of fragments of an array of ECM proteins, including those of the basement membrane, has revealed a complex pathological scenario caused by the direct action of SVMPs...
October 22, 2016: Toxins
Gabriela Berg, Verónica Miksztowicz, Celina Morales, Magalí Barchuk, Graciela López, Ricardo Póveda, Ricardo Gelpi, Laura Schreier, Miguel Rubio
BACKGROUND: Epicardial adipose tissue (EAT) is a visceral adipose tissue (AT) surrounding and infiltrating myocardium and coronary arteries. Increased EAT may represent a chronic inflammatory injury and represent a link with coronary artery disease (CAD). Metalloproteinases (MMPs) are involved in expansion of AT. OBJECTIVE: to evaluate MMP-2 and -9 behavior in EAT from coronary artery disease patients. METHODS: In EAT and subcutaneous AT (SAT) from patients undergoing coronary artery bypass graft (CABG, n=30) or valve replacement (No CABG, n=18), MMP-2 and -9 activity and localization, inflammatory cells and vascular endothelial growth factor (VEGF) levels were determined...
October 24, 2016: Current Vascular Pharmacology
Robert Jin-Hong Chang, Dimitri T Azar, Kyu-Yeon Han
Vascular endothelial growth factor receptor 3 (VEGFR3) regulates the growth and differentiation of blood and lymphatic vessels. To determine whether matrix metalloproteinase 14 (MMP14) modulates VEGFR3 expression in the corneal epithelium to influence the avascularity of the cornea, VEGFR3 expression was compared between wild-type and MMP14-deficient (MMP14 Δexon4) corneal epithelial cells. Western blot analysis showed that VEGFR3 protein expression was higher on MMP14 Δexon4 corneal epithelial cells than on wild-type cells, and quantitative RT-PCR analysis showed that VEGFR3 gene expression was highly induced in MMP14 Δexon4 corneal epithelial cells but not in wild-type corneal epithelial cells or wild-type and MMP14 Δexon4 corneal keratocytes...
October 24, 2016: Protein and Peptide Letters
Ratana Lim, Gillian Barker, Stella Liong, Caitlyn Nguyen-Ngo, Stephen Tong, Tu'uhevaha Kaitu'u-Lino, Martha Lappas
INTRODUCTION: Infection and inflammation stimulate pro-inflammatory cytokines, prostaglandins and matrix metalloproteinase (MMP)-9, which play a central role in myometrial contractions and rupture of fetal membranes. In human and mouse immune cells, activating transcription factor 3 (ATF3) is a negative regulator of inflammation. No studies have examined the role of ATF3 in human labour. METHODS: Primary amnion cells were used to determine the effect of interleukin (IL)-1β and the bacterial product fibroblast-stimulating lipopeptide (fsl-1) on ATF3 expression, and the effect of ATF3 siRNA on pro-labour mediators...
November 2016: Placenta
Srilata Puru Naik, Mahesh P A, Jayaraj B S, SubbaRao V Madhunapantula, Sareh Raeiszadeh Jahromi, Manish Kumar Yadav
INTRODUCTION: Even though IL-6 and MMP-9 are associated with airway inflammation in asthma, there is paucity of data in Indian population. OBJECTIVE: To determine the levels of IL-6 and MMP-9 in the serum of patients suffering from asthma, and correlate with (a) disease severity, as per GINA guidelines; (b) clinical phenotypes; and (c) response to treatment. METHODOLOGY: The levels of IL-6 and MMP-9 were compared between moderate persistent asthma (n = 25), severe persistent asthma (n = 25) and normal controls (n = 30)...
October 26, 2016: Journal of Asthma: Official Journal of the Association for the Care of Asthma
Harcharan K Rooprai, Andrew J Martin, Andrew King, Usha D Appadu, Huw Jones, Richard P Selway, Richard W Gullan, Geoffrey J Pilkington
MMPs (matrix metalloproteinases), ADAMs (a disintegrin and metalloproteinase) and TIMPs (tissue inhibitors of metalloproteinases) are implicated in invasion and angiogenesis: both are tissue remodeling processes involving regulated proteolysis of the extracellular matrix, growth factors and their receptors. The expression of these three groups and their correlations with clinical behaviour has been reported in gliomas but a similar comprehensive study in meningiomas is lacking. In this study, we aimed to evaluate the patterns of expression of 23 MMPs, 4 TIMPs, 8 ADAMs, selective growth factors and their receptors in 17 benign meningiomas using a quantitative real-time polymerase chain reaction (qPCR)...
October 18, 2016: International Journal of Oncology
Hong-Xia Cui, Honglan Wang, Yuchun Wang, Juan Song, Hua Tian, Chunhui Xia, Yetong Shen
Changes in the carbohydrate structure on the surface of tumor cells is an important feature of cancer metastasis. The specific role of sialic acids in the glycoconjugate terminal has not yet been clearly elucidated in these processes. Previously, we reported that α2,3-sialic acid residues in breast cancer are associated with metastatic potential. The α2,3-sialyltransferase ST3Gal III, which adds α2,3-sialic acids to glycoproteins, is overexpressed in various tumors, and enzyme activity is correlated with tumor metastasis, yet its mechanistic role has not been fully evaluated...
October 18, 2016: Oncology Reports
Min Xu, Hailang Zhou, Chunli Zhang, Junbo He, Hong Wei, Meng Zhou, Ying Lu, Yaocheng Sun, Jerry Wanming Ding, Jian Zeng, Wanxin Peng, Fengyi Du, Aihua Gong
Although a disintegrin and metalloproteinase-17 (ADAM17) overexpression has been demonstrated in numerous human tumors including gastric cancer, its role in gastric cancer development remains to be clarified. In the present study, we identify that ADAM17 activates TGF-β/Smad signaling to promote epithelial-mesenchymal transition (EMT) in gastric cancer cells. We found that ADAM17 promotes proliferation, migration and invasion in gastric carcinoma cells. Subsequently, we revealed that silencing ADAM17 induces the expression of epithelial marker of E-cadherin and downregulates expression of mesenchymal markers including N-cadherin, vimentin and Snail in MGC803 and MKN45 cells, whereas ADAM17 overexpression reverses these changes in BGC823 and HGC27 cells...
October 21, 2016: International Journal of Oncology
Yusaku Osako, Naohiko Seki, Yoshiaki Kita, Keiichi Yonemori, Keiichi Koshizuka, Akira Kurozumi, Itaru Omoto, Ken Sasaki, Yasuto Uchikado, Hiroshi Kurahara, Kosei Maemura, Shoji Natsugoe
Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive malignancies. Recently developed molecular targeted therapies are not available for patients with ESCC. After curative surgical resection, patients frequently suffer distant metastasis and recurrence. Exploration of novel ESCC metastatic pathways may lead to the development of new treatment protocols for this disease. Accordingly, we have sequentially identified microRNA (miRNA)-mediated metastatic pathways in several cancers. Our past studies of miRNA expression signatures have shown that microRNA-375 (miR-375) is frequently reduced in several types of cancers, including ESCC...
October 21, 2016: International Journal of Oncology
Stuart A Cain, Ewa J Mularczyk, Mukti Singh, Teresa Massam-Wu, Cay M Kielty
ADAMTS10 and ADAMTS6 are homologous metalloproteinases with ill-defined roles. ADAMTS10 mutations cause Weill-Marchesani syndrome (WMS), implicating it in fibrillin microfibril biology since some fibrillin-1 mutations also cause WMS. However little is known about ADAMTS6 function. ADAMTS10 is resistant to furin cleavage, however we show that ADAMTS6 is effectively processed and active. Using siRNA, over-expression and mutagenesis, it was found ADAMTS6 inhibits and ADAMTS10 is required for focal adhesions, epithelial cell-cell junction formation, and microfibril deposition...
October 25, 2016: Scientific Reports
Xiao-Na Zhou, Guang-Ming Li, Ying-Chen Xu, Tuan-Jie Zhao, Ji-Xiang Wu
BACKGROUND: Decoy receptor 3 (DcR3) binds to Fas ligand (FasL) and inhibits FasL-induced apoptosis. The receptor is overexpressed in hepatocellular carcinoma (HCC), and it is associated with the growth and metastatic spread of tumors. DcR3 holds promises as a new target for the treatment of HCC, but little is known regarding the molecular mechanisms underlying the oncogenic properties of DcR3. The present work, therefore, examined the role of DcR3 in regulating the growth and invasive property of liver cancer cell HepG2...
2016: Chinese Medical Journal
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