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https://www.readbyqxmd.com/read/28342779/suppression-of-calpain-expression-by-nsaids-is-associated-with-inhibition-of-cell-migration-in-rat-duodenum
#1
Kristopher Silver, A Littlejohn, Laurel Thomas, Bhupinder Bawa, James D Lillich
Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for the alleviation of pain and inflammation, but these drugs are also associated with a suite of negative side effects. Gastrointestinal (GI) toxicity is particularly concerning since it affects an estimated 70% of individuals taking NSAIDs routinely, and evidence suggests the majority of toxicity is occurring in the small intestine. Traditionally, NSAID-induced GI toxicity has been associated with indiscriminate inhibition of cyclooxygenase isoforms, but other mechanisms, including inhibition of cell migration, intestinal restitution, and wound healing, are likely to contribute to toxicity...
March 22, 2017: Toxicology
https://www.readbyqxmd.com/read/28337562/bace2-suppression-promotes-%C3%AE-cell-survival-and-function-in-a-model-of-type-2-diabetes-induced-by-human-islet-amyloid-polypeptide-overexpression
#2
Gema Alcarraz-Vizán, Carlos Castaño, Montse Visa, Joel Montane, Joan-Marc Servitja, Anna Novials
BACE2 (β-site APP-cleaving enzyme 2) is a protease expressed in the brain, but also in the pancreas, where it seems to play a physiological role. Amyloidogenic diseases, including Alzheimer's disease and type 2 diabetes (T2D), share the accumulation of abnormally folded and insoluble proteins that interfere with cell function. In T2D, islet amyloid polypeptide (IAPP) deposits have been shown to be a pathogenic key feature of the disease. The aim of the present study was to investigate the effect of BACE2 modulation on β-cell alterations in a mouse model of T2D induced by IAPP overexpression...
March 23, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28336948/plasminogen-activator-inhibitor-1-protects-mice-against-cardiac-fibrosis-by-inhibiting-urokinase-type-plasminogen-activator-mediated-plasminogen-activation
#3
Kamlesh K Gupta, Deborah L Donahue, Mayra J Sandoval-Cooper, Francis J Castellino, Victoria A Ploplis
Plasminogen activator inhibitor-1 (PAI-1) is known to protect mice against cardiac fibrosis. It has been speculated that PAI-1 may regulate cardiac fibrosis by inactivating urokinase-type plasminogen activator (uPA) and ultimately plasmin (Pm) generation. However, the in vivo role of PAI-1 in inactivating uPA and limiting the generation of Pm during cardiac fibrosis remains to be established. The objective of this study was to determine if the cardioprotective effect of PAI-1 is mediated through its ability to directly regulate urokinase -mediated activation of plasminogen (Pg)...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28326151/chronic-porphyromonas-gingivalis-infection-accelerates-the-occurrence-of-age-related-granules-in-apoe-mice-brains
#4
Sim K Singhrao, Sasanka Chukkapalli, Sophie Poole, Irina Velsko, St John Crean, Lakshmyya Kesavalu
This study explored the origin of age-related granules in the apolipoprotein E gene knockout (ApoE(-/-)) B6 background mice brains following chronic gingival infection with Porphyromonas gingivalis for 24 weeks. Intracerebral localization of P. gingivalis was detected by fluorescence in situ hybridization (FISH) and its protease by immunohistochemistry. The age-related granules were observed by periodic acid-Schiff (PAS), silver impregnation, and immunostaining. FISH showed intracerebral dissemination of P...
2017: Journal of Oral Microbiology
https://www.readbyqxmd.com/read/28326083/the-small-tellurium-compound-as101-ameliorates-rat-crescentic-glomerulonephritis-association-with-inhibition-of-macrophage-caspase-1-activity-via-very-late-antigen-4-inactivation
#5
Yafit Hachmo, Yona Kalechman, Itai Skornick, Uzi Gafter, Rachel R Caspi, Benjamin Sredni
Crescentic glomerulonephritis (CGN) is the most aggressive form of GN and, if untreated, patients can progress to end-stage renal failure within weeks of presentation. The α4β1 integrin very late antigen-4 (VLA-4) is an adhesion molecule of fundamental importance to the recruitment of leukocytes in inflammation. We addressed the role of VLA-4 in mediating progressive renal injury in a rat model of CGN using a small tellurium compound. AS101 [ammonium trichloro(dioxoethylene-o,o')tellurate]. This compound has been previously shown to uniquely inhibit VLA-4 activity by redox inactivation of adjacent thiols in the exofacial domain of VLA-4...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28323866/elevated-fecal-peptidase-d-at-onset-of-colitis-in-galphai2-mice-a-mouse-model-of-ibd
#6
Daniel Bergemalm, Robert Kruse, Maria Sapnara, Jonas Halfvarson, Elisabeth Hultgren Hörnquist
BACKGROUND: The identification of novel fecal biomarkers in inflammatory bowel disease (IBD) is hampered by the complexity of the human fecal proteome. On the other hand, in experimental mouse models there is probably less variation. We investigated the fecal protein content in mice to identify possible biomarkers and pathogenic mechanisms. METHODS: Fecal samples were collected at onset of inflammation in Galphai2-/- mice, a well-described spontaneous model of chronic colitis, and from healthy littermates...
2017: PloS One
https://www.readbyqxmd.com/read/28320709/plasmin-and-plasminogen-induce-macrophage-reprogramming-and-regulate-key-steps-of-inflammation-resolution-via-annexin-a1
#7
Michelle A Sugimoto, Ana Luíza C Ribeiro, Bruno R C Costa, Juliana P Vago, Kátia M Lima, Fernanda S Carneiro, Mylena Maira O Ortiz, Graziele Letícia N Lima, Aline A F Carmo, Renata M Rocha, Denise A Perez, Alessandra C Reis, Vanessa Pinho, Lindsey A Miles, Cristiana C Garcia, Mauro M Teixeira, Lirlândia P Sousa
Inflammation resolution is an active process that functions to restore tissue homeostasis. Participation of the plasminogen/plasmin (Plg/Pla) system in the productive phase of inflammation is well known, but its involvement in the resolution phase remains unclear. Therefore, we aimed to investigate the potential role of Plg/Pla in key events during the resolution of acute inflammation and its underlying mechanisms. Plg/Pla injection into the pleural cavity of BALB/c mice induced a time-dependent influx of mononuclear cells that were primarily macrophages of anti-inflammatory (M2 - F4/80(high) Gr1(-) CD11b(high)) and proresolving (Mres - F4/80(med) CD11b(low)) phenotypes, without changing the number of macrophages with a pro-inflammatory profile (M1 - F4/80(low) Gr1(+) CD11b(med))...
March 20, 2017: Blood
https://www.readbyqxmd.com/read/28315357/therapeutic-potential-of-krait-venom
#8
Antony Gomes, Partha Pratim Saha, Shamik Bhattacharya, Sourav Ghosh, Aparna Gomes
Kraits belong to Elapideae and are widely distributed in East and South-East Asian countries. Krait venom possesses neurotoxins, membrane toxins, cardiotoxins, three finger toxins, metalloproteinases, cholinesterases, L-amino acid oxidases and serine proteases. The therapeutic potential of krait venom in pathophysiological conditions such as microbial and parasitic infections, cancer, arthritis, inflammation and blood coagulation disorder is discussed in this review. More intensive new research ventures are required to establish the therapeutic potential of krait venom in complex and emerging diseases...
March 14, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28314697/demeanor-of-rivaroxaban-in-activated-inactivated-fxa
#9
Kaname Seki, Yosuke Mizuno, Toku Sakashita, Shintaro Nakano, Jun Tanno, Yasushi Okazaki, Toshihiro Muramatsu, Shigeyuki Nishimura, Takaaki Senbonmatsu
Activated factor X (FXa) plays an important role in thrombin generation and inflammation. Factor X is not converted constitutively to FXa, but only after intrinsic clotting factors are activated and/or cellular injury occurs. Although rivaroxaban is one of direct FXa inhibitors, its function in the inactivated coagulation cascade is unclear. In human umbilical vein endothelial cells that natively express protease-activated receptor-1 and -2, high dose rivaroxaban did not alter gene transcripts including pro-inflammatory genes in DNA microarray...
February 24, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28298913/cathepsin-e-deficiency-ameliorates-graft-versus-host-disease-and-modifies-dendritic-cell-motility
#10
Jörg Mengwasser, Liane Babes, Steffen Cordes, Sarah Mertlitz, Katarina Riesner, Yu Shi, Aleixandria McGearey, Martina Kalupa, Thomas Reinheckel, Olaf Penack
Microbial products influence immunity after allogeneic hematopoietic stem cell transplantation (allo-SCT). In this context, the role of cathepsin E (Ctse), an aspartate protease known to cleave bacterial peptides for antigen presentation in dendritic cells (DCs), has not been studied. During experimental acute graft-versus-host disease (GVHD), we found infiltration by Ctse-positive immune cells leading to higher Ctse RNA- and protein levels in target organs. In Ctse-deficient allo-SCT recipients, we found ameliorated GVHD, improved survival, and lower numbers of tissue-infiltrating DCs...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28298400/antimicrobial-peptide-levels-are-linked-to-airway-inflammation-bacterial-colonisation-and-exacerbations-in-chronic-obstructive-pulmonary-disease
#11
Louise J P Persson, Marianne Aanerud, Jon A Hardie, Roy Miodini Nilsen, Per S Bakke, Tomas M Eagan, Pieter S Hiemstra
Antimicrobial peptides (AMPs) are effectors of host defence against infection, inflammation and wound repair. We aimed to study AMP levels in stable chronic obstructive pulmonary disease (COPD) and during acute exacerbations of COPD (AECOPD), and to examine their relation to clinical parameters and inflammatory markers.The 3-year Bergen COPD Cohort Study included 433 COPD patients and 325 controls. Induced sputum was obtained and analysed for levels of the AMPs human cathelicidin (hCAP18/LL-37) and secretory leukocyte protease inhibitor (SLPI), and for the inflammatory markers interleukin (IL)-8, IL-6 and tumour necrosis factor-α (TNF-α) using immunoassays...
March 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/28296821/protease-activated-receptor-1-plays-a-proinflammatory-role-in-colitis-by-promoting-th17-related-immunity
#12
Muhammad A Saeed, Garrett Z Ng, Jan Däbritz, Josef Wagner, Louise Judd, Jia-Xi Han, Poshmaal Dhar, Carl D Kirkwood, Philip Sutton
BACKGROUND: Proteolytic cleavage of protease-activated receptor 1 (PAR1) can result in potent downstream regulatory effects on inflammation. Although PAR1 is expressed throughout the gastrointestinal tract and activating proteases are increased in inflammatory bowel disease, the effect of PAR1 activation on colitis remains poorly understood, and has not previously been studied in pediatric disease. METHODS: Expression of PAR1 and inflammatory cytokines in colonic biopsies from pediatric patients with Crohn's disease exhibiting active moderate to severe colitis was measured by quantitative PCR...
April 2017: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/28295446/a-recombinant-cystatin-from-ascaris-lumbricoides-attenuates-inflammation-of-dss-induced-colitis
#13
Sandra Coronado, Luis Barrios, Josefina Zakzuk, Ronald Regino, Velky Ahumada, Luis Franco, Yanet Ocampo, Luis Caraballo
Helminthiasis may ameliorate inflammatory diseases, such as inflammatory bowel disease and asthma. Information about immunomodulators from Ascaris lumbricoides is scarce, but could be important considering the co-evolutionary relationships between helminths and humans. We evaluated the immunomodulatory effects of a recombinant cystatin from A. lumbricoides on an acute model of Dextran Sodium Sulphate (DSS)-induced colitis in mice. From an A. lumbricoides cDNA library we obtained a recombinant cystatin (rAl-CPI)...
March 10, 2017: Parasite Immunology
https://www.readbyqxmd.com/read/28289191/cathepsin-s-is-the-major-activator-of-the-psoriasis-associated-proinflammatory-cytokine-il-36%C3%AE
#14
Joseph S Ainscough, Tom Macleod, Dennis McGonagle, Rosella Brakefield, Jens M Baron, Ade Alase, Miriam Wittmann, Martin Stacey
The proinflammatory cytokine IL-36γ is highly expressed in epithelial cells and is a pivotal mediator of epithelial inflammation. In particular, IL-36γ is strongly associated with the inflammatory skin disease psoriasis. As with other IL-1 cytokines, IL-36γ is expressed as an inactive precursor and must be processed by specific proteases to become bioactive. Our aim therefore was to identify protease/s capable of IL-36γ activation and explore the importance of this activation in psoriasis. Using a keratinocyte-based activity assay in conjunction with small-molecule inhibitors and siRNA gene silencing, cathepsin S was identified as the major IL-36γ-activating protease expressed by epithelial cells...
March 13, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28276434/extracellular-proteasome-osteopontin-circuit-regulates-cell-migration-with-implications-in-multiple-sclerosis
#15
Chiara Dianzani, Elena Bellavista, Juliane Liepe, Claudia Verderio, Morena Martucci, Aurelia Santoro, Annalisa Chiocchetti, Casimiro Luca Gigliotti, Elena Boggio, Benedetta Ferrara, Loredana Riganti, Christin Keller, Katharina Janek, Agathe Niewienda, Chiara Fenoglio, Melissa Sorosina, Roberto Cantello, Peter M Kloetzel, Michael P H Stumpf, Friedemann Paul, Klemens Ruprecht, Daniela Galimberti, Filippo Martinelli Boneschi, Cristoforo Comi, Umberto Dianzani, Michele Mishto
Osteopontin is a pleiotropic cytokine that is involved in several diseases including multiple sclerosis. Secreted osteopontin is cleaved by few known proteases, modulating its pro-inflammatory activities. Here we show by in vitro experiments that secreted osteopontin can be processed by extracellular proteasomes, thereby producing fragments with novel chemotactic activity. Furthermore, osteopontin reduces the release of proteasomes in the extracellular space. The latter phenomenon seems to occur in vivo in multiple sclerosis, where it reflects the remission/relapse alternation...
March 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28270702/unconventional-role-of-caspase-6-in-spinal-microglia-activation-and-chronic-pain
#16
REVIEW
Temugin Berta, Jee Eun Lee, Chul-Kyu Park
Chronic pain affects ~20% of the worldwide population. The clinical management of chronic pain is mostly palliative and results in limited success. Current treatments mostly target the symptoms or neuronal signaling of chronic pain. It has been increasingly recognized that glial cells, such as microglia, and inflammatory signaling play a major role in the pathogenesis of chronic pain. Caspases (CASPs) are a family of protease enzymes involved in apoptosis and inflammation. They are pivotal components in a variety of neurological diseases...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28265034/extracellular-matrix-inflammation-in-vascular-cognitive-impairment-and-dementia
#17
REVIEW
Gary A Rosenberg
Vascular cognitive impairment and dementia (VCID) include a wide spectrum of chronic manifestations of vascular disease related to large vessel strokes and small vessel disease (SVD). Lacunar strokes and white matter (WM) injury are consequences of SVD. The main vascular risk factor for SVD is brain hypoperfusion from cerebral blood vessel narrowing due to chronic hypertension. The hypoperfusion leads to activation and degeneration of astrocytes with the resulting fibrosis of the extracellular matrix (ECM)...
March 1, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28264498/retinoic-acid-negatively-impacts-proliferation-and-mctc-specific-attributes-of-human-skin-derived-mast-cells-but-reinforces-allergic-stimulability
#18
Magda Babina, Metin Artuc, Sven Guhl, Torsten Zuberbier
The Vitamin-A-metabolite retinoic acid (RA) acts as a master regulator of cellular programs. Mast cells (MCs) are primary effector cells of type-I-allergic reactions. We recently uncovered that human cutaneous MCs are enriched with RA network components over other skin cells. Yet, direct experimental evidence on the significance of the RA-MC axis is limited. Here, skin-derived cultured MCs were exposed to RA for seven days and investigated by flow-cytometry (BrdU incorporation, Annexin/PI, FcεRI), microscopy, RT-qPCR, histamine quantitation, protease activity, and degranulation assays...
February 28, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28262770/fecal-bacterial-communities-in-treated-hiv-infected-individuals-on-two-antiretroviral-regimens
#19
Sandra Pinto-Cardoso, Catherine Lozupone, Olivia Briceño, Selma Alva-Hernández, Norma Téllez, Aguilar Adriana, Akio Murakami-Ogasawara, Gustavo Reyes-Terán
Intestinal microbiome changes that occur in HIV positive individuals on different antiretroviral therapy (ART) regimens are important to understand, as they are potentially linked with chronic inflammation and microbiome-linked comorbidities that occur at increased incidence in this population. We conducted a cross-sectional study comparing the fecal microbiomes of HIV-uninfected (HIV SN) to HIV-infected individuals on long-term ART (HIV+ LTART) from Mexico using 16S ribosomal RNA (16sRNA) targeted sequencing...
March 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28260878/effect-of-simvastatin-on-mmps-and-timps-in-cigarette-smoke-induced-rat-copd-model
#20
Jiawei Sun, Jie Bao, Yanan Shi, Bin Zhang, Lindong Yuan, Junhong Li, Lihai Zhang, Mo Sun, Ling Zhang, Wuzhuang Sun
BACKGROUND: Proteases may play an important role in the development of chronic obstructive pulmonary disease and emphysema in response to cigarette smoke exposure (CSE). The current study was designed to investigate the expression of matrix metalloproteinase (MMP)-8, MMP-9, MMP-12, tissue inhibitor of MMP (TIMP)-1, and TIMP-4 in rat lung tissues in response to CSE, and assessed the effect of simvastatin in regulating expression of MMPs and TIMPs. METHODS: Thirty normal Sprague Dawley (SD) rats were divided into control (n=10), CSE (n=10), and CSE plus simvastatin (n=10) groups...
2017: International Journal of Chronic Obstructive Pulmonary Disease
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