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https://www.readbyqxmd.com/read/29779119/a-chemosensitizer-drug-disulfiram-prevents-doxorubicin-induced-cardiac-dysfunction-and-oxidative-stress-in-rats
#1
Varsha K Sonawane, Umesh B Mahajan, Sachin D Shinde, Subhajit Chatterjee, Sandip S Chaudhari, Harshada A Bhangale, Shreesh Ojha, Sameer N Goyal, Chanakya N Kundu, Chandragouda R Patil
In the present study, the preventive effects of orally administered disulfiram (DS) against the doxorubicin (DOX)-induced cardiotoxicity were investigated in rats. DS was orally administered for 7 days at doses of 2, 10, and 50 mg/kg/day. DOX (30 mg/kg) was intraperitoneally administered on the 5th day of the initiation of DS treatment. Within 48 h of injection, DOX treatment significantly altered ECG, elevated the ST height, and increased the QT and QRS intervals. It reduced the cardiac levels of injury markers like creatine kinase isoenzyme-MB and lactate dehydrogenase...
May 10, 2018: Cardiovascular Toxicology
https://www.readbyqxmd.com/read/29778882/insight-into-the-interactions-of-proteinase-inhibitor-alpha-2-macroglobulin-with-hypochlorite-thermal-analysis-and-biophysical-approach
#2
Tooba Siddiqui, Mohammad Khalid Zia, Syed Saqib Ali, Haseeb Ahsan, Fahim Halim Khan
Hypochlorous acid, an active bleaching agent is one of the major oxidants produced by neutrophils under physiological conditions. It is a potent reactive oxygen species (ROS) which causes oxidation of biomolecules. Treatment of proteins with hypochlorite results in direct oxidative damage to proteins. Alpha-2-macroglobulin is a major proteinase inhibitor and it can inhibit proteinase of any kind regardless of specificity and catalytic mechanism. The proteinase-antiproteinase balance plays an important role in mediating inflammation associated tissue destruction...
May 17, 2018: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29778674/innate-effector-cells-in-angiogenesis-and-lymphangiogenesis
#3
REVIEW
Gilda Varricchi, Stefania Loffredo, Maria Rosaria Galdiero, Giancarlo Marone, Leonardo Cristinziano, Francescopaolo Granata, Gianni Marone
Angiogenesis and lymphangiogenesis are distinct and complex processes requiring a finely tuned balance between stimulatory and inhibitory signals. During adulthood, angiogenesis and lymphangiogenesis are activated at sites of tumor growth, tissue injury and remodeling, and chronic inflammation. Vascular endothelial growth factors (VEGFs), angiopoietin (ANGPTs) and a multitude of additional signaling molecules play distinct roles in the modulation of angiogenesis/lymphangiogenesis. VEGFs and ANGPTs activate specific tyrosine kinase receptor (e...
May 17, 2018: Current Opinion in Immunology
https://www.readbyqxmd.com/read/29777224/progression-of-whole-blood-transcriptional-signatures-from-interferon-induced-to-neutrophil-associated-patterns-in-severe-influenza
#4
Jake Dunning, Simon Blankley, Long T Hoang, Mike Cox, Christine M Graham, Philip L James, Chloe I Bloom, Damien Chaussabel, Jacques Banchereau, Stephen J Brett, Miriam F Moffatt, Anne O'Garra, Peter J M Openshaw
Transcriptional profiles and host-response biomarkers are used increasingly to investigate the severity, subtype and pathogenesis of disease. We now describe whole-blood mRNA signatures and concentrations of local and systemic immunological mediators in 131 adults hospitalized with influenza, from whom extensive clinical and investigational data were obtained by MOSAIC investigators. Signatures reflective of interferon-related antiviral pathways were common up to day 4 of symptoms in patients who did not require mechanical ventilator support; in those who needed mechanical ventilation, an inflammatory, activated-neutrophil and cell-stress or death ('bacterial') pattern was seen, even early in disease...
May 18, 2018: Nature Immunology
https://www.readbyqxmd.com/read/29776812/preservation-with-%C3%AE-1-antitrypsin-improves-primary-graft-function-of-murine-lung-transplants
#5
Jessica Götzfried, Natalia F Smirnova, Carmela Morrone, Brice Korkmaz, Ali Önder Yildirim, Oliver Eickelberg, Dieter E Jenne
BACKGROUND: Vascular damage and primary graft dysfunction increase with prolonged preservation times of transplanted donor lungs. Hence, storage and conservation of donated lungs in protein-free, dextran-containing electrolyte solutions, like Perfadex, is limited to about 6 hours. We hypothesized that transplanted lungs are protected against neutrophil-mediated proteolytic damage by adding α1 -anti-trypsin (AAT), a highly abundant human plasma proteinase inhibitor, to Perfadex. METHODS: A realistic clinically oriented murine model of lung transplantation was used to simulate the ischemia-reperfusion process...
March 30, 2018: Journal of Heart and Lung Transplantation
https://www.readbyqxmd.com/read/29776751/development-of-an-opsonophagocytic-killing-assay-for-group-a-streptococcus
#6
Scott Jones, Nicole J Moreland, Marta Zancolli, Jeremy Raynes, Jacelyn M S Loh, Pierre R Smeesters, Shiranee Sriskandan, Jonathan R Carapetis, John D Fraser, David Goldblatt
Group A Streptococcus (GAS) or Streptococcus pyogenes is responsible for an estimated 500,000 deaths worldwide each year. Protection against GAS infection is thought to be mediated by phagocytosis, enhanced by bacteria-specific antibody. There are no licenced GAS vaccines, despite many promising candidates in preclinical and early stage clinical development, the most advanced of which are based on the GAS M-protein. Vaccine progress has been hindered, in part, by the lack of a standardised functional assay suitable for vaccine evaluation...
May 15, 2018: Vaccine
https://www.readbyqxmd.com/read/29776451/myeloid-specific-tak1-deletion-results-in-reduced-brain-monocyte-infiltration-and-improved-outcomes-after-stroke
#7
Anjali Chauhan, Jacob Hudobenko, Abdullah Al Mamun, Edward C Koellhoffer, Anthony Patrizz, Rodney M Ritzel, Bhanu P Ganesh, Louise D McCullough
BACKGROUND: Activation of transforming growth factor-β-activated kinase 1 (TAK1) occurs after stroke and leads to an exacerbation of brain injury. TAK1 is involved in innate and adaptive immune responses, but it has divergent inflammatory effects that are dependent on the cell type in which it is activated. There is a robust infiltration of myeloid cells after stroke; however, the contribution of myeloid TAK1 to cerebral ischemia is currently unknown. We hypothesized that myeloid-specific deletion of TAK1 would protect against ischemic brain injury...
May 17, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29775893/puerarin-prevents-vascular-endothelial-injury-through-suppression-of-nf-%C3%AE%C2%BAb-activation-in-lps-challenged-human-umbilical-vein-endothelial-cells
#8
Hua-Fei Deng, Sha Wang, Lian Li, Qin Zhou, Wan-Bei Guo, Xiao-Li Wang, Mei-Dong Liu, Ke Liu, Xian-Zhong Xiao
OBJECTIVE: In the present study, we aimed to explore the effects of puerarin on vascular endothelial cell injury induced by lipopolysaccharide (LPS) and its underlying mechanisms. METHODS: The cell viability and morphological changes were assessed using the cell counting kit-8 (CCK-8) assay and 4´,6-diamidino-2-phenylindole (DAPI) staining, respectively. The levels of tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), monocyte/macrophage chemotactic protein-1 (MCP-1), IL-8, intercellular cell adhesion molecule-1 (ICAM-1), thrombomodulin (TM) and plasminogen activator inhibitor-1 (PAI-1) in cell culture supernatant were determined by the enzyme-linked immunosorbent assay (ELISA)...
May 15, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29775738/humoral-and-mucosal-immune-responses-in-meagre-argyrosomus-regius-juveniles-fed-diets-with-varying-inclusion-levels-of-carob-seed-germ-meal
#9
Francisco Antonio Guardiola, Carolina Barroso, Paula Enes, Ana Couto, Patricia Díaz-Rosales, António Afonso, Erika Kanashiro, Helena Peres, Elisabete Matos, Aires Oliva-Teles, Pedro Pousão-Ferreira, Benjamín Costas
Many studies have assessed the effects of incorporation of plant feedstuffs in fish diets on growth performance, whereas few studies have addressed the effects of fish meal replacement by plant protein sources on fish immune parameters. Thus, the aim of this study was to evaluate the effects on immune response of different inclusion levels of carob seed germ meal (CSGM) as partial replacement for fish meal in diets for meagre (Argyrosomus regius) juveniles. Fish were fed four experimental diets with increased CSGM inclusion levels [0% (control), 7...
May 15, 2018: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/29774526/retrotransposable-genetic-elements-causing-neutrophil-defects
#10
REVIEW
Dirk Roos, Martin de Boer
Retrotransposable elements are stretches of DNA that encode proteins with the inherent ability to insert their own RNA or another RNA by reverse transcriptase as DNA into a new genomic location. In humans, the only autonomous retrotransposable elements are members of the Long INterspersed Element-1 (LINE-1) family. LINE-1s may cause gene inactivation and human disease. We present a brief summary of the published knowledge about LINE-1s in humans and the RNAs that these elements can transpose, and we focus on the effect of LINE-1-mediated retrotransposition on human neutrophil function...
May 17, 2018: European Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29773851/modeling-transcriptional-rewiring-in-neutrophils-through-the-course-of-treated-juvenile-idiopathic-arthritis
#11
Zihua Hu, Kaiyu Jiang, Mark Barton Frank, Yanmin Chen, James N Jarvis
Neutrophils in children with the polyarticular form of juvenile idiopathic arthritis (JIA) display abnormal transcriptional patterns linked to fundamental metabolic derangements. In this study, we sought to determine the effects of therapy on mRNA and miRNA expression networks in polyarticular JIA. Using exon and miRNA microarrays, we studied children with untreated active JIA (ADU, n = 35), children with active disease on therapy with methotrexate ± etanercept (ADT, n = 26), and children with inactive disease also on therapy (ID, n = 14)...
May 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29773794/calreticulin-and-integrin-alpha-dissociation-induces-anti-inflammatory-programming-in-animal-models-of-inflammatory-bowel-disease
#12
Masayoshi Ohkuro, Jun-Dal Kim, Yoshikazu Kuboi, Yuki Hayashi, Hayase Mizukami, Hiroko Kobayashi-Kuramochi, Kenzo Muramoto, Manabu Shirato, Fumiko Michikawa-Tanaka, Jun Moriya, Teruya Kozaki, Kazuma Takase, Kenichi Chiba, Kishan Lal Agarwala, Takayuki Kimura, Makoto Kotake, Tetsuya Kawahara, Naoki Yoneda, Shinsuke Hirota, Hiroshi Azuma, Nobuko Ozasa-Komura, Yoshiaki Ohashi, Masafumi Muratani, Keiji Kimura, Ieharu Hishinuma, Akiyoshi Fukamizu
Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, is a chronic intestinal inflammatory condition initiated by integrins-mediated leukocyte adhesion to the activated colonic microvascular endothelium. Calreticulin (CRT), a calcium-binding chaperone, is known as a partner in the activation of integrin α subunits (ITGAs). The relationship between their interaction and the pathogenesis of IBD is largely unknown. Here we show that a small molecule, orally active ER-464195-01, inhibits the CRT binding to ITGAs, which suppresses the adhesiveness of both T cells and neutrophils...
May 17, 2018: Nature Communications
https://www.readbyqxmd.com/read/29773345/t-cells-and-their-immunometabolism-a-novel-way-to-understanding-sepsis-immunopathogenesis-and-future-therapeutics
#13
REVIEW
V Kumar
Sepsis has always been considered as a big challenge for pharmaceutical companies in terms of discovering and designing new therapeutics. The pathogenesis of sepsis involves aberrant activation of innate immune cells (i.e. macrophages, neutrophils etc.) at early stages. However, a stage of immunosuppression is also observed during sepsis even in the patients who have recovered from it. This stage of immunosuppression is observed due to the loss of conventional (i.e. CD4+ , CD8+ ) T cells, Th17 cells and an upregulation of regulatory T cells (Tregs)...
May 5, 2018: European Journal of Cell Biology
https://www.readbyqxmd.com/read/29772553/establishment-of-a-porcine-model-of-indomethacin-induced-intestinal-injury
#14
Dan Yi, Wenkai Liu, Yongqing Hou, Lei Wang, Di Zhao, Tao Wu, Binying Ding, Guoyao Wu
A useful animal model of intestinal injury is pivotal for studying its pathogenesis and developing nutritional interventions (e.g., amino acid supplementation). Here, we propose the use of indomethacin (IDMT) to induce intestinal inflammation in neonatal pigs. Fourteen-day-old piglets fed a milk replacer diet receive intraperitoneal administration of IDMT (5 mg/kg body weight) for 3 consecutive days. On day 4, blood and intestinal samples are obtained for physiological and biochemical analyses. IDMT increases blood DAO activity, I-FABP concentration, neutrophil and eosinophil numbers; intestinal MMP3 mRNA levels, MPO activity, and MDA concentration; but reduces the plasma concentration of citrulline (synthesized exclusively by enterocytes of the small intestine), intestinal GSH-Px activity, and mRNA levels for villin , I-FABP , TRPV6 , AQP10 , and KCNJ13 ...
June 1, 2018: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/29772343/brain-stimulation-differentially-modulates-nociception-and-inflammation-in-aversive-and-non-aversive-behavioural-conditions
#15
G S Bassi, A Kanashiro, G J Rodrigues, F Q Cunha, N C Coimbra, L Ulloa
Inflammation and pain are major clinical burdens contributing to multiple disorders and limiting the quality of life of patients. We previously reported that brain electrical stimulation can attenuate joint inflammation in experimental arthritis. Here, we report that non-aversive electrical stimulation of the locus coeruleus (LC), the paraventricular hypothalamic nucleus (PVN) or the ventrolateral column of the periaqueductal grey matter (vlPAG) decreases thermal pain sensitivity, knee inflammation and synovial neutrophilic infiltration in ratswith intra-articular zymosan...
May 14, 2018: Neuroscience
https://www.readbyqxmd.com/read/29772024/use-of-human-amniotic-epithelial-cells-in-mouse-models-of-bleomycin-induced-lung-fibrosis-a-systematic-review-and-meta-analysis
#16
Fang He, Aiting Zhou, Shuo Feng
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) urgently requires effective treatment. Bleomycin-induced lung injury models are characterized by initial inflammation and secondary fibrosis, consistent with the pathological features of IPF. Human amniotic epithelial cells (hAECs) exhibit good differentiation potential and paracrine activity and are thus ideal for cell-based clinical therapies. The therapeutic effects of hAECs on lung fibrosis are attributed to many factors. We performed a systematic review of preclinical studies investigating the treatment of pulmonary fibrosis with hAECs to provide suggestions for their clinical use...
2018: PloS One
https://www.readbyqxmd.com/read/29771768/high-density-infiltration-of-v-domain-immunoglobulin-suppressor-of-t-cell-activation-up-regulated-immune-cells-in-human-pancreatic-cancer
#17
Jinʼe Liu, Xiaoxue Xie, Chunxiao Xuan, Tingting Li, Lanlan Wang, Lianghong Teng, Jun Liu
V-domain immunoglobulin suppressor of T-cell activation (VISTA) is constitutively expressed in hematopoietic lineage and is highly up-regulated in tumor infiltrated myeloid cells and regulatory T cells in animal models. However, its expression in human pancreatic tumor microenvironment remains unknown. In this research, we aimed at the expression of VISTA in human pancreatic cancer samples. METHODS: We performed immunohistochemistry to determine VISTA expression in human pancreatic cancer samples...
May 15, 2018: Pancreas
https://www.readbyqxmd.com/read/29771572/inhibition-of-ubiquitin-activating-enzyme-protects-against-organ-injury-after-intestinal-ischemia-reperfusion
#18
Shingo Matsuo, Andrew Chaung, Deanna Liou, Ping Wang, Weng-Lang Yang
Intestinal ischemia-reperfusion (I/R) occurs in various clinical settings, such as transplantation, acute mesenteric arterial occlusion, trauma and shock. I/R injury causes severe systemic inflammation, leading to multiple organ dysfunction associated with high mortality. The ubiquitin proteasome pathway has been indicated in the regulation of inflammation, particularly through NF-κB signaling pathway. PYR-41 is a small molecular compound that selectively inhibits ubiquitin-activating enzyme E1. A mouse model of intestinal I/R injury by clamping the superior mesenteric artery for 45 minutes was performed to evaluate the effect of PYR-41 treatment on organ injury and inflammation...
May 17, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/29770125/fgf23-actions-on-target-tissues-with-and-without-klotho
#19
REVIEW
Beatrice Richter, Christian Faul
Fibroblast growth factor (FGF) 23 is a phosphaturic hormone whose physiologic actions on target tissues are mediated by FGF receptors (FGFR) and klotho, which functions as a co-receptor that increases the binding affinity of FGF23 for FGFRs. By stimulating FGFR/klotho complexes in the kidney and parathyroid gland, FGF23 reduces renal phosphate uptake and secretion of parathyroid hormone, respectively, thereby acting as a key regulator of phosphate metabolism. Recently, it has been shown that FGF23 can also target cell types that lack klotho...
2018: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29769642/high-resolution-imaging-of-myeloperoxidase-activity-sensors-in-human-cerebrovascular-disease
#20
Youssef Z Wadghiri, Dung Minh Hoang, Anita Leporati, Matthew J Gounis, Aurora Rodríguez-Rodríguez, Mary L Mazzanti, John P Weaver, Ajay K Wakhloo, Peter Caravan, Alexei A Bogdanov
Progress in clinical development of magnetic resonance imaging (MRI) substrate-sensors of enzymatic activity has been slow partly due to the lack of human efficacy data. We report here a strategy that may serve as a shortcut from bench to bedside. We tested ultra high-resolution 7T MRI (µMRI) of human surgical histology sections in a 3-year IRB approved, HIPAA compliant study of surgically clipped brain aneurysms. µMRI was used for assessing the efficacy of MRI substrate-sensors that detect myeloperoxidase activity in inflammation...
May 16, 2018: Scientific Reports
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