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https://www.readbyqxmd.com/read/29352570/the-nlrp3-inflammasome-and-the-emerging-role-of-colchicine-to-inhibit-atherosclerosis-associated-inflammation
#1
REVIEW
Gonzalo J Martínez, David S Celermajer, Sanjay Patel
Atherosclerosis is considered a chronic inflammatory disease of the arterial wall. Recently, compelling evidence has arisen for the role of monocytes and neutrophils and a particular protein complex that resides within these cells - the NLRP3 inflammasome - in atherosclerosis-associated inflammation. It is now also known that cholesterol crystals are present through all stages of atherosclerosis and can activate the NLRP3 inflammasome within these inflammatory cells to produce interleukin 1β and interleukin 18 - key mediators in the inflammatory cascade that drive plaque progression and instability...
December 25, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/29352287/ifn%C3%AE-inhibits-g-csf-induced-neutrophil-expansion-and-invasion-of-the-cns-to-prevent-viral-encephalitis
#2
Chandran Ramakrishna, Edouard M Cantin
Emergency hematopoiesis facilitates the rapid expansion of inflammatory immune cells in response to infections by pathogens, a process that must be carefully regulated to prevent potentially life threatening inflammatory responses. Here, we describe a novel regulatory role for the cytokine IFNγ that is critical for preventing fatal encephalitis after viral infection. HSV1 encephalitis (HSE) is triggered by the invasion of the brainstem by inflammatory monocytes and neutrophils. In mice lacking IFNγ (GKO), we observed unrestrained increases in G-CSF levels but not in GM-CSF or IL-17...
January 19, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29351812/a-hybrid-protein-containing-msp1a-repeats-and-omp7-omp8-and-omp9-epitopes-protect-immunized-balb-c-mice-against-anaplasmosis
#3
Alex Sander R Cangussu, Luis André M Mariúba, Pritesh Lalwani, Keila Dayane E S Pereira, Spartaco Astolphi-Filho, Patricia P Orlandi, Sabrina Epiphanio, Kelvison F Viana, Mucio Flavio B Ribeiro, Hidelberto M Silva, Claudio R F Marinho, Paulo A Nogueira
Anaplasma marginale (A. marginale) has a remarkable impact on livestock production, and an effective vaccine is not currently available due to the inexistence of a small animal model. Recently, BALB/c mice were successfully infected with A. marginale, resulting in an acute and persistent anaplasmosis infection. Here, we designed a hybrid protein containing repeats of polypeptide 1a from major surface protein-1 complex (MSP1a) repeats and common epitopes of outer membrane proteins (OMPs) OMP7, OMP8 and OMP9 expressed in Escherichia coli...
January 19, 2018: Veterinary Research
https://www.readbyqxmd.com/read/29351721/myeloperoxidase-and-neurological-disorder-a-cross-talk
#4
Kanta Pravalika, Deepaneeta Sarmah, Harpreet Kaur, Madhuri Wanve, Jackson Saraf, Kiran Kalia, Anupom Borah, Dileep R Yavagal, Kunjan R Dave, Pallab Bhattacharya
Myeloperoxidase (MPO) is a protein present in azurophilic granules, macrophages, and neutrophils that are released into extracellular fluid (ECF) during inflammation. MPO releases hypochlorous acid (HOCL) and other chlorinated species. It is derived from hydrogen peroxide (H2O2) showing response during inflammatory conditions and plays a role in the immune defense against pathogens. MPO may show unwanted effects by indirectly increasing the formation of reactive nitrogen species (RNS), reactive oxygen species (ROS), and tumor necrosis factor alpha (TNF-α) leading to inflammation and oxidative stress...
January 19, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29351622/antimicrobial-peptide-resistance-mechanism-contributes-to-staphylococcus-aureus-infection
#5
Gordon Y C Cheung, Emilie L Fisher, Joshua W McCausland, Justin Choi, John W M Collins, Seth W Dickey, Michael Otto
Antimicrobial peptides (AMPs) constitute an important part of innate host defense. Possibly limiting the therapeutic potential of AMPs is the fact that bacteria have developed AMP resistance mechanisms during their co-evolution with humans. However, there is no direct evidence that AMP resistance per se is important during an infection. Here we show that the Staphylococcus aureus Pmt ABC transporter defends the bacteria from killing by important human AMPs and elimination by human neutrophils. By showing that Pmt contributes to virulence during skin infection in an AMP-dependent manner, we provide evidence that AMP resistance plays a key role in bacterial infection...
January 17, 2018: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29351567/whole-thorax-irradiation-of-non-human-primates-induces-persistent-nuclear-damage-and-gene-expression-changes-in-peripheral-blood-cells
#6
Shanaz A Ghandhi, Helen C Turner, Igor Shuryak, Gregory O Dugan, J Daniel Bourland, John D Olson, Janet A Tooze, Shad R Morton, Ines Batinic-Haberle, J Mark Cline, Sally A Amundson
We investigated the cytogenetic and gene expression responses of peripheral blood cells of non-human primates (NHP, Macaca mulatta) that were whole-thorax irradiated with a single dose of 10 Gy. In this model, partial irradiation of NHPs in the thoracic region (Whole Thorax Lung Irradiation, WTLI) allows the study of late radiation-induced lung injury, while avoiding acute radiation syndromes related to hematopoietic and gastrointestinal injury. A transient drop in circulating lymphocytes and platelets was seen by 9 days, followed by elevations in respiratory rate, circulating neutrophils, lymphocytes, and monocytes at 60-100 days, corresponding to computed tomography (CT) and histologic evidence of pneumonitis, and elective euthanasia of four animals...
2018: PloS One
https://www.readbyqxmd.com/read/29351433/%C3%AE-nitrostyrene-derivatives-attenuate-lps-mediated-acute-lung-injury-via-the-inhibition-of-neutrophil-platelet-interactions-and-net-release
#7
Yao-Wen Chang, Ching-Ping Tseng, Chih-Hsun Lee, Tsong-Long Hwang, Yu-Li Chen, Mei-Tzu Su, Kowit-Yu Chong, Ying-Wei Lan, Chin-Chung Wu, Kung-Ju Chen, Fen-Hua Lu, Hsiang-Ruei Liao, Chuen Hsueh, Pei-Wen Hsieh
Acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS) are high-mortality and life-threatening diseases that are associated with neutrophil activation and accumulation within lung tissue. Emerging evidence indicates that neutrophil-platelet aggregates (NPAs) at sites of injury increases acute inflammation and contributes to the development of ALI. Even though numerous studies have increased our understanding of the pathophysiology of ALI, there is still a lack of innovative and useful treatments that reduce mortality, emphasizing that there is an urgent need for novel treatment strategies...
January 11, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29350834/proton-pump-inhibitors-elevate-infection-rate-in-cardiothoracic-surgery-patients-by-influencing-pmn-function-in-vitro-and-in-vivo
#8
Carolin Maria Haas, Martina Maywald, Andreas Goetzenich, Christian Stoppe, Lothar Rink
Proton-pump inhibitors (PPI) as pantoprazole are highly effective acid suppressive agents that belong to the world's most sold medication. However, they are pronounced to have immunosuppressive aspects. In our study, a negative influence of PPI on functions of polymorphonuclear cells in vitro like phagocytosis, oxidative burst, chemotaxis, and killing activity was shown, whereas formation of neutrophil extracellular traps (NET)osis remained unaffected. Pantoprazole stimulation additionally reduced the production of the proinflammatory cytokine IL-1β in whole blood assay as well as the production of IL-2 and IFN-γ after whole blood stimulation with phytohaemagglutinin...
January 19, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29350771/recombinant-relaxin-protects-liver-transplants-from-ischemia-damage-via-hepatocyte-glucocorticoid-receptor-from-bench-to-bedside
#9
Shoichi Kageyama, Kojiro Nakamura, Takehiro Fujii, Bibo Ke, Rebecca A Sosa, Elaine F Reed, Nakul Datta, Ali Zarrinpar, Ronald W Busuttil, Jerzy W Kupiec-Weglinski
Hepatic ischemia-reperfusion injury (IRI) represents a major risk factor of early graft dysfunction and acute/chronic rejection as well as a key obstacle to expanding the donor pool in orthotopic liver transplantation (OLT). Although glucocorticoid receptor (GR) signaling may enhance cytoprotective programs, clinical use of glucocorticoid is limited due to adverse effects, while clinical relevance of GR-facilitated cytoprotection in OLT remains unknown. We aimed to evaluate the significance of hepatic GR in clinical OLT and verify the impact of recombinant human relaxin (rhRLX), which may function as GR agonist in tissue/disease-specific manner...
January 19, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29350745/tio2-nanoparticles-can-selectively-bind-cxcl8-impacting-on-neutrophil-chemotaxis
#10
J Batt, M Milward, I Chapple, M Grant, H Roberts, O Addison
The interaction between TiO2 nanoparticles (NPs) and inflammatory cytokines, including CXCL8, a clinically relevant pro-inflammatory chemokine was investigated. TiO2 is present in tissues adjacent to failing implanted Ti (titanium) devices. TiO2 NPs were shown to bind to CXCL8 in vitro, causing perturbation of quantification of CXCL8 by ELISA, in both simple and complex protein panels, in a dose-dependent manner. Binding between TiO2 NPs and CXCL8 was demonstrated by protein gel electrophoresis. TiO2 NPs were also shown to inactivate the chemoattractant property of CXCL8 in a dose-dependent manner, suggesting that the binding between TiO2 NPs and CXCL8 is likely to be clinically relevant...
January 19, 2018: European Cells & Materials
https://www.readbyqxmd.com/read/29350282/neutrophil-chemotaxis
#11
REVIEW
Björn Petri, Maria-Jesús Sanz
Neutrophils are the primary cells recruited to inflamed sites during an innate immune response to tissue damage and/or infection. They are finely sensitive to inciting stimuli to reach in great numbers and within minutes areas of inflammation and tissue insult. For this effective response, they can detect extracellular chemical gradients and move towards higher concentrations, the so-called chemotaxis process or guided cell migration. This directed neutrophil recruitment is orchestrated by chemoattractants, a chemically diverse group of molecular guidance cues (e...
January 19, 2018: Cell and Tissue Research
https://www.readbyqxmd.com/read/29349917/risk-stratification-for-febrile-neutropenia-in-patients-with-testicular-germ-cell-tumors
#12
Angelika Terbuch, Florian Posch, Richard Partl, Brigitte Zurl, Thomas Bauernhofer, Martin Pichler, Joanna Szkandera, Georg C Hutterer, Karl Pummer, Karin S Kapp, Herbert Stöger, Armin Gerger, Michael Stotz
The aim of this study was to detect risk factors for febrile neutropenia (FN) in patients with testicular germ cell tumors (TGCT). In this retrospective cohort study at the Medical University of Graz, we included 413 consecutive TGCT patients who received adjuvant or curative treatment with cisplatin-based chemotherapy. FN occurred in 70 (16.9%) of 413 patients. In univariable logistic regression, higher age (odds ratio (OR) per 5 years = 1.17, 95% CI: 1.02-1.35, P = 0.022), reduced performance status (PS) (OR = 2...
January 19, 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29348638/changes-in-cytokine-responses-to-tb-antigens-esat-6-cfp-10-and-tb-7-7-and-inflammatory-markers-in-peripheral-blood-during-therapy
#13
Ah Young Leem, Joo Han Song, Eun Hye Lee, Hyejon Lee, Bora Sim, Song Yee Kim, Kyung Soo Chung, Eun Young Kim, Ji Ye Jung, Moo Suk Park, Young Sam Kim, Joon Chang, Young Ae Kang
Multiple cytokines and inflammatory markers control TB infection. We aimed to investigate the changes in multiple cytokines and inflammatory markers in active TB patients following anti-TB drug therapy. Twenty-nine patients with active TB were recruited prospectively between December 2010 and July 2017. Blood samples were collected before (T0), after 2 months (T2), and at the end of anti-TB treatment (Tend). We measured the levels of Interferon (IFN)-γ, interleukin (IL)-2, IL-12, IL-10, IL-13 and tumor necrosis factor (TNF)-α in supernatants collected from the QuantiFERON-TB Gold In-Tube assay (QFT-GIT), as well as the WBC, neutrophil, platelet count and neutrophil to lymphocyte ratio (NLR) in whole blood...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29348630/expression-of-inflammasome-proteins-and-inflammasome-activation-occurs-in-human-but-not-in-murine-keratinocytes
#14
Jennifer Sand, Eric Haertel, Thomas Biedermann, Emmanuel Contassot, Ernst Reichmann, Lars E French, Sabine Werner, Hans-Dietmar Beer
Inflammasomes are multimeric protein complexes that assemble upon sensing of a variety of stress factors. Their formation results in caspase-1-mediated activation and secretion of the pro-inflammatory cytokines pro-interleukin(IL)-1β and -18, which induce an inflammatory response. Inflammation is supported by a lytic form of cell death, termed pyroptosis. Innate immune cells, such as macrophages or dendritic cells, express and activate inflammasomes. However, it has also been demonstrated that human primary keratinocytes activate different types of inflammasomes in vitro, for example, upon UVB irradiation or viral infection...
January 18, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29348570/systematic-in-vivo-evaluation-of-the-time-dependent-inflammatory-response-to-steel-and-teflon-insulin-infusion-catheters
#15
Jasmin R Hauzenberger, Julia Münzker, Petra Kotzbeck, Martin Asslaber, Vladimir Bubalo, Jeffrey I Joseph, Thomas R Pieber
Continuous subcutaneous insulin infusion (CSII) catheters are considered the weak link of insulin pump therapy. Wear-time considerably varies between patients and the choice of catheter material is based on personal preferences rather than scientific facts. Therefore, we systematically assessed and quantified the inflammatory tissue response to steel versus Teflon CSII catheters over a maximum wear-time of 7 days in swine. Tissue surrounding catheters was analysed using histopathology and quantitative real-time PCR...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29348500/myeloid-derived-suppressor-cells-coming-of-age
#16
REVIEW
Filippo Veglia, Michela Perego, Dmitry Gabrilovich
Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of cells generated during a large array of pathologic conditions ranging from cancer to obesity. These cells represent a pathologic state of activation of monocytes and relatively immature neutrophils. MDSCs are characterized by a distinct set of genomic and biochemical features, and can, on the basis of recent findings, be distinguished by specific surface molecules. The salient feature of these cells is their ability to inhibit T cell function and thus contribute to the pathogenesis of various diseases...
January 18, 2018: Nature Immunology
https://www.readbyqxmd.com/read/29348297/changes-in-macrophage-transcriptome-associate-with-systemic-sclerosis-and-mediate-gsdma-contribution-to-disease-risk
#17
Aida Moreno-Moral, Marta Bagnati, Surya Koturan, Jeong-Hun Ko, Carmen Fonseca, Nathan Harmston, Laurence Game, Javier Martin, Voon Ong, David J Abraham, Christopher P Denton, Jacques Behmoaras, Enrico Petretto
OBJECTIVES: Several common and rare risk variants have been reported for systemic sclerosis (SSc), but the effector cell(s) mediating the function of these genetic variants remains to be elucidated. While innate immune cells have been proposed as the critical targets to interfere with the disease process underlying SSc, no studies have comprehensively established their effector role. Here we investigated the contribution of monocyte-derived macrophages (MDMs) in mediating genetic susceptibility to SSc...
January 17, 2018: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/29348121/endothelial-cell-derived-von-willebrand-factor-but-not-platelet-derived-promotes-atherosclerosis-in-apolipoprotein-e-deficient-mice
#18
Prakash Doddapattar, Nirav Dhanesha, Mehul R Chorawala, Chandler Tinsman, Manish Jain, Manasa K Nayak, Janice M Staber, Anil K Chauhan
OBJECTIVE: VWF (von Willebrand factor) is synthesized by endothelial cells and megakaryocytes and is known to contribute to atherosclerosis. In vitro studies suggest that platelet-derived VWF (Plt-VWF) is biochemically and functionally different from endothelial cell-derived VWF (EC-VWF). We determined the role of different pools of VWF in the pathophysiology of atherosclerosis. APPROACH AND RESULTS: Using bone marrow transplantation, we generated chimeric Plt-VWF, EC-VWF, and Plt-VWF mice lacking a disintegrin and metalloprotease with thrombospondin type I repeats-13 in platelets and plasma on apolipoprotein E-deficient (Apoe-/-) background...
January 18, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29346422/nanoparticle-effect-on-neutrophil-produced-myeloperoxidase
#19
Elodie Sanfins, Alexandra Correia, Stefan B Gunnarsson, Manuel Vilanova, Tommy Cedervall
Nanoparticles affect the immune system as they may interact directly with immune cells and activate them. However, it is possible that nanoparticles also interact with released cytokines and immunologically active enzymes. To test this hypothesis, the activity of myeloperoxidase released from activated neutrophils was measured in the presence of nanoparticles with different chemistry and size. In high concentrations of nanoparticles, myeloperoxidase activity is decreased whereas in low concentrations of nanoparticles the activity is increased...
2018: PloS One
https://www.readbyqxmd.com/read/29346149/testing-elevated-protease-activity-prospective-analysis-of-160-wounds
#20
Anike Lockmann, Tillmann Schill, Franziska Hartmann, Lisa-Lena Grönemeyer, Ricarda Holzkamp, Michael P Schön, Kai-Martin Thoms
OBJECTIVE: Given that local elevated protease activity (EPA) has been implicated in impaired wound healing, a prospective single-center study was conducted to assess protease activity in various wound types. METHODS: Protease activity was determined using an easy-to-use test system (Woundchek Protease Status Test Kit; Systagenix, Gatwick, United Kingdom) in 160 wounds in 143 patients. The assay detects the combined activity of inflammatory proteases, mainly matrix metalloproteinases 8 and 9 and human neutrophil elastase...
February 2018: Advances in Skin & Wound Care
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