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https://www.readbyqxmd.com/read/28453734/novel-targets-and-future-strategies-for-acute-cardioprotection-position-paper-of-the-european-society-of-cardiology-working-group-on-cellular-biology-of-the-heart
#1
Derek J Hausenloy, David Garcia-Dorado, Hans Erik Bøtker, Sean M Davidson, James Downey, Felix B Engel, Robert Jennings, Sandrine Lecour, Jonathan Leor, Rosalinda Madonna, Michel Ovize, Cinzia Perrino, Fabrice Prunier, Rainer Schulz, Joost P G Sluijter, Linda W Van Laake, Jakob Vinten-Johansen, Derek M Yellon, Kirsti Ytrehus, Gerd Heusch, Péter Ferdinandy
Ischaemic heart disease and the heart failure that often results, remain the leading causes of death and disability in Europe and worldwide. As such, in order to prevent heart failure and improve clinical outcomes in patients presenting with an acute ST-segment elevation myocardial infarction and patients undergoing coronary artery bypass graft surgery, novel therapies are required to protect the heart against the detrimental effects of acute ischaemia/reperfusion injury (IRI). During the last three decades, a wide variety of ischaemic conditioning strategies and pharmacological treatments have been tested in the clinic-however, their translation from experimental to clinical studies for improving patient outcomes has been both challenging and disappointing...
May 1, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28453725/serelaxin-treatment-promotes-adaptive-hypertrophy-but-does-not-prevent-heart-failure-in-experimental-peripartum-cardiomyopathy
#2
Justus Nonhoff, Melanie Ricke-Hoch, Mirco Mueller, Britta Stapel, Tobias Pfeffer, Martina Kasten, Michaela Scherr, Constantin von Kaisenberg, Johann Bauersachs, Arash Haghikia, Denise Hilfiker-Kleiner
Aims: Peripartum cardiomyopathy (PPCM) is a systolic left ventricular dysfunction developing in the peripartum phase in previously healthy women. Relaxin-2 is a pregnancy hormone with potential beneficial effects in heart failure patients. We evaluated Relaxin-2 as a potential diagnostic marker and/or a therapeutic agent in PPCM. Methods and results: In healthy peripartum women, serum Relaxin-2 levels (measured by ELISA in the second half of pregnancy) were elevated showing a decreasing trend in the first postpartum week and returned to non-pregnant levels thereafter...
May 1, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28453640/pioneering-topological-methods-for-network-based-drug-target-prediction-by-exploiting-a-brain-network-self-organization-theory
#3
Claudio Durán, Simone Daminelli, Josephine M Thomas, V Joachim Haupt, Michael Schroeder, Carlo Vittorio Cannistraci
The bipartite network representation of the drug-target interactions (DTIs) in a biosystem enhances understanding of the drugs' multifaceted action modes, suggests therapeutic switching for approved drugs and unveils possible side effects. As experimental testing of DTIs is costly and time-consuming, computational predictors are of great aid. Here, for the first time, state-of-the-art DTI supervised predictors custom-made in network biology were compared-using standard and innovative validation frameworks-with unsupervised pure topological-based models designed for general-purpose link prediction in bipartite networks...
April 26, 2017: Briefings in Bioinformatics
https://www.readbyqxmd.com/read/28448237/regulatory-t-cell-therapy-for-uveitis-a-new-promising-challenge
#4
Arnaud Foussat, Sylvie Gregoire, Nathalie Clerget-Chossat, Celine Terrada, Hélène Asnagli, François M Lemoine, David Klatzmann, Phuc LeHoang, Miguel Forte, Bahram Bodaghi
Uveitis is a sight-threatening primary intraocular inflammation of various origins in mainly young and active patients. Due to the absence of biomarkers in most of the cases, the current treatment of noninfectious entities remains nonspecific, using corticosteroids, conventional immunosuppressors, and more recently biological agents. Identification of regulatory T cells in different models of autoimmune uveitis together with the evaluation of this important subpopulation in different entities paved the way for new therapeutic strategies, in addition to exclusive pharmaceutical approaches...
May 2017: Journal of Ocular Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28447731/vatalanib-a-tyrosine-kinase-inhibitor-decreases-hepatic-fibrosis-and-sinusoidal-capillarization-in-ccl4-induced-fibrotic-mice
#5
Ling-Jian Kong, Hao Li, Ya-Ju Du, Feng-Hua Pei, Ying Hu, Liao-Liao Zhao, Jing Chen
Among the various consequence arising from lung injury, hepatic fibrosis is the most severe. Decreasing the effects of hepatic fibrosis remains one of the primary therapeutic challenges in hepatology. Dysfunction of hepatic sinusoidal endothelial cells is considered to be one of the initial events that occur in liver injury. Vascular endothelial growth factor signaling is involved in the progression of genotype changes. The aim of the present study was to determine the effect of the tyrosine kinase inhibitor, vatalanib, on hepatic fibrosis and hepatic sinusoidal capillarization in a carbon tetrachloride (CCl4)‑induced mouse model of liver fibrosis...
March 15, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28447547/urinary-bladder-extracellular-matrix-hydrogels-and-matrix-bound-vesicles-differentially-regulate-central-nervous-system-neuron-viability-and-axon-growth-and-branching
#6
Anne Faust, Apoorva Kandakatla, Yolandi van der Merwe, Tanchen Ren, Luai Huleihel, George Hussey, Juan Diego Naranjo, Scott Johnson, Stephen Badylak, Michael Steketee
Central nervous system neurons often degenerate after trauma due to the inflammatory innate immune response to injury, which can lead to neuronal cell death, scarring, and permanently lost neurologic function. Extracellular matrix bioscaffolds, derived by decellularizing healthy tissues, have been widely used in both preclinical and clinical studies to promote positive tissue remodeling, including neurogenesis, in numerous tissues, with extracellular matrix from homologous tissues often inducing more positive responses...
April 2017: Journal of Biomaterials Applications
https://www.readbyqxmd.com/read/28447115/human-genetics-as-a-model-for-target-validation-finding-new-therapies-for-diabetes
#7
REVIEW
Soren K Thomsen, Anna L Gloyn
Type 2 diabetes is a global epidemic with major effects on healthcare expenditure and quality of life. Currently available treatments are inadequate for the prevention of comorbidities, yet progress towards new therapies remains slow. A major barrier is the insufficiency of traditional preclinical models for predicting drug efficacy and safety. Human genetics offers a complementary model to assess causal mechanisms for target validation. Genetic perturbations are 'experiments of nature' that provide a uniquely relevant window into the long-term effects of modulating specific targets...
April 26, 2017: Diabetologia
https://www.readbyqxmd.com/read/28446968/the-role-of-transforming-growth-factor-tgf-%C3%AE-in-the-infarcted-myocardium
#8
REVIEW
Nikolaos G Frangogiannis
The adult mammalian heart has negligible regenerative capacity. Following myocardial infarction, sudden necrosis of cardiomyocytes triggers an intense inflammatory reaction that clears the wound from dead cells and matrix debris, while activating a reparative program. A growing body of evidence suggests that members of the transforming growth factor (TGF)-β family critically regulate the inflammatory and reparative response following infarction. Although all three TGF-β isoforms (TGF-β1, -β2 and -β3) are markedly upregulated in the infarcted myocardium, information on isoform-specific actions is limited...
March 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28446910/are-mast-cells-masters-in-cancer
#9
REVIEW
Gilda Varricchi, Maria Rosaria Galdiero, Stefania Loffredo, Giancarlo Marone, Raffaella Iannone, Gianni Marone, Francescopaolo Granata
Prolonged low-grade inflammation or smoldering inflammation is a hallmark of cancer. Mast cells form a heterogeneous population of immune cells with differences in their ultra-structure, morphology, mediator content, and surface receptors. Mast cells are widely distributed throughout all tissues and are stromal components of the inflammatory microenvironment that modulates tumor initiation and development. Although canonically associated with allergic disorders, mast cells are a major source of pro-tumorigenic (e...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28446773/therapeutic-effects-of-anti-hmgb1-monoclonal-antibody-on-pilocarpine-induced-status-epilepticus-in-mice
#10
Li Fu, Keyue Liu, Hidenori Wake, Kiyoshi Teshigawara, Tadashi Yoshino, Hideo Takahashi, Shuji Mori, Masahiro Nishibori
Inflammatory processes in brain tissue have been described in human epilepsy of various etiologies and in experimental models of seizures. High mobility group box-1 (HMGB1) is now recognized as representative of damage-associated molecular patterns (DAMPs). In the present study, we focused on whether anti-HMGB1 antibody treatment could relieve status epilepticus- triggered BBB breakdown and inflammation response in addition to the seizure behavior itself. Pilocarpine and methyl-scopolamine were used to establish the acute seizure model...
April 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28446565/murinization-and-h-chain-isotype-matching-of-the-anti-gitr-antibody-dta-1-reduces-immunogenicity-mediated-anaphylaxis-in-c57bl-6-mice
#11
Nicole A Belmar, Sarah W Chan, Melvin I Fox, Josue A Samayoa, Marcia M Stickler, Ninian N Tran, Yoshiko Akamatsu, Diane Hollenbaugh, Fiona A Harding, Hamsell M Alvarez
Recent advances in immuno-oncology have shown that the immune system can be activated to induce long-term, durable antitumor responses. For immuno-oncology drug development, immune activation is often explored using rat Abs in immunocompetent mouse models. Although these models can be used to show efficacy, antidrug immune responses to experimental protein-based therapeutics can arise. Immunogenicity of surrogate Abs may therefore represent an important obstacle to the evaluation of the antitumor efficacy of immunomodulator Abs in syngeneic models...
April 26, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28446517/a-novel-%C3%AE-calcitonin-gene-related-peptide-analogue-protects-against-end-organ-damage-in-experimental-hypertension-cardiac-hypertrophy-and-heart-failure
#12
Aisah A Aubdool, Pratish Thakore, Fulye Argunhan, Sarah-Jane Smillie, Moritz Schnelle, Salil Srivastava, Khadija M Alawi, Elena Wilde, Jennifer Mitchell, Keith Farrell-Dillon, Daniel A Richards, Giuseppe Maltese, Richard C Siow, Manasi Nandi, James E Clark, Ajay M Shah, Anette Sams, Susan D Brain
Background -Research into the therapeutic potential of α-calcitonin gene-related peptide (α-CGRP) has been limited due to its peptide nature and short half-life. Here, we evaluate whether a novel potent and long lasting (t½ ≥ 7h) acylated α-CGRP analogue (αAnalogue) could alleviate and reverse cardiovascular disease in two distinct murine models of hypertension and heart failure in vivoMethods -The ability of the αAnalogue to act selectively via the CGRP pathway was shown in skin using a CGRP receptor antagonist...
April 26, 2017: Circulation
https://www.readbyqxmd.com/read/28446504/feasibility-of-ultra-high-throughput-functional-screening-of-melanoma-biopsies-for-discovery-of-novel-cancer-drug-combinations
#13
Adam A Friedman, Yun Xia, Lorenzo Trippa, Long P Le, Vivien Igras, Dennie T Frederick, Jennifer A Wargo, Kenneth K Tanabe, Donald P Lawrence, Donna S Neuberg, Keith T Flaherty, David Fisher
Purpose: Successful development of targeted therapy combinations for cancer patients depends on first discovering such combinations in predictive preclinical models. Stable cell lines and mouse xenograft models can have genetic and phenotypic drift and may take too long to generate to be useful as a personalized medicine tool. <p>Experimental Design: To overcome these limitations, we have used a platform of ultra-high-throughput functional screening of primary biopsies preserving both cancer and stroma cell populations from melanoma patients to nominate such novel combinations from a library of  thousands of drug combinations in a patient-specific manner within days of biopsy...
April 26, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28446216/the-effect-of-adipose-tissue-derived-stem-cells-in-a-middle-cerebral-artery-occlusion-stroke-model-depends-on-their-engraftment-rate
#14
Saskia Grudzenski, Sebastian Baier, Anne Ebert, Pim Pullens, Andreas Lemke, Karen Bieback, Rick M Dijkhuizen, Lothar R Schad, Angelika Alonso, Michael G Hennerici, Marc Fatar
BACKGROUND: In the field of experimental stem cell therapy, intra-arterial (IA) delivery yields the best results concerning, for example, migrated cell number at the targeted site. However, IA application also appears to be associated with increased mortality rates and infarction. Since many rodent studies systemically apply 1 × 10(6) cells, this could also be a consequence of engrafted cell number. The aim of this study was therefore to investigate the effect of different doses of adipose tissue-derived stem cells (ASCs) on engraftment rates and stroke outcome measured in vivo using 9...
April 26, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28446179/glycam1-negatively-regulates-monocyte-entry-into-the-optic-nerve-head-and-contributes-to-radiation-based-protection-in-glaucoma
#15
Pete A Williams, Catherine E Braine, Nicole E Foxworth, Kelly E Cochran, Simon W M John
BACKGROUND: We previously reported a profound long-term neuroprotection subsequent to a single radiation-therapy in the DBA/2J mouse model of glaucoma. This neuroprotection prevents entry of monocyte-like immune cells into the optic nerve head during glaucoma. Gene expression studies in radiation-treated mice implicated Glycam1 in this protection. Glycam1 encodes a proteoglycan ligand for L-selectin and is an excellent candidate to modulate immune cell entry into the eye. Here, we experimentally test the hypothesis that radiation-induced over-expression of Glycam1 is a key component of the neuroprotection...
April 26, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28445245/ectopic-expression-of-innate-immune-protein-lipocalin-2-in-lactococcus-lactis-protects-against-gut-and-environmental-stressors
#16
Piu Saha, Benoit Chassaing, Beng San Yeoh, Emilie Viennois, Xia Xiao, Mary J Kennett, Vishal Singh, Matam Vijay-Kumar
BACKGROUND: Lipocalin-2 (Lcn2) is a multifunctional innate immune protein that exhibits antimicrobial activity by the sequestration of bacterial siderophores, regulates iron homeostasis, and augments cellular tolerance to oxidative stress. Studies in the murine model of colitis have demonstrated that Lcn2 deficiency exacerbates colitogenesis; however, the therapeutic potential of Lcn2 supplementation has yet to be elucidated. In light of its potential mucoprotective functions, we, herein, investigated whether expression of Lcn2 in the probiotic bacterium can be exploited to alleviate experimental colitis...
April 25, 2017: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/28445239/aldosterone-and-vascular-mineralocorticoid-receptors-in-murine-endotoxic-and-human-septic-shock
#17
Fouad Fadel, Gwennan André-Grégoire, Basile Gravez, Brigitte Bauvois, Sandrine Bouchet, Catalina Sierra-Ramos, Andrea Polito, Arnaud Mansart, Diego Alvarez de la Rosa, Djillali Annane, Frédéric Jaisser
OBJECTIVES: Vascular mineralocorticoid receptors play a role in vascular tone and blood pressure regulation, might participate in the pathophysiology of circulatory failure during sepsis, and represent a potential therapeutic target in this disease. We aimed to study the effects of mineralocorticoids and the involvement of vascular mineralocorticoid receptors in murine endotoxic and human septic shock. DESIGN: Experimental study. SETTING: Translational investigation including animal research and in vitro experiments using human vascular cells and plasma from septic patients...
April 25, 2017: Critical Care Medicine
https://www.readbyqxmd.com/read/28444128/low-dose-ionizing-radiation-induces-therapeutic-neovascularization-in-a-pre-clinical-model-of-hindlimb-ischemia
#18
Augusto Ministro, Paula de Oliveira, Raquel J Nunes, André Dos Santos Rocha, Adriana Correia, Tânia Carvalho, José Rino, Pedro Faísca, Jorg D Becker, J Goyri-O'Neill, Filomena Pina, Esmeralda Poli, Bruno Silva-Santos, Fausto Pinto, Marc Mareel, Karine Serre, Susana Constantino Rosa Santos
We have previously shown that low-dose ionizing radiation (LDIR) induces angiogenesis but there is no evidence that they induce neovascularization in the setting of peripheral arterial disease. Here, we investigated the use of LDIR as an innovative and non-invasive strategy to stimulate therapeutic neovascularization using a model of experimentally induced hindlimb ischemia (HLI). Methods and results: After surgical induction of unilateral HLI, both hindlimbs of female C57BL/6 mice were sham-irradiated or irradiated with four daily fractions of 0...
April 19, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28443564/transpulmonary-hypothermia-with-cooled-oxygen-inhalation-shows-promising-results-as-a-novel-hypothermia-technique
#19
Yahya Ayhan Acar, Banu Karakuş Yılmaz, Duygu Sultan Çelik, Erdem Çevik, Hatice Topçu, Şule Özsoy, Aylin Haklıgör, Orhan Çınar
BACKGROUND: Therapeutic hypothermia was showed to improve neurologic outcome but current therapeutic hypothermia techniques have limitations. Novel techniques such as transpulmonary hypothermia with cooled oxygen inhalation may be beneficial. AIMS: To evaluate the performance of transthoracic hypothermia with cooled medical oxygen inhalation as a therapeutic hypothermia method. STUDY DESIGN: Animal experimentation. METHODS: A total of 36 adult male Wistar-Hannover rats were used in this research...
April 6, 2017: Balkan Medical Journal
https://www.readbyqxmd.com/read/28443249/francisella-tularensis-susceptibility-to-antibiotics-a-comprehensive-review-of-the-data-obtained-in-vitro-and-in-animal-models
#20
REVIEW
Yvan Caspar, Max Maurin
The antibiotic classes that are recommended for tularaemia treatment are the aminoglycosides, the fluoroquinolones and the tetracyclines. However, cure rates vary between 60 and 100% depending on the antibiotic used, the time to appropriate antibiotic therapy setup and its duration, and the presence of complications, such as lymph node suppuration. Thus, antibiotic susceptibility testing (AST) of F. tularensis strains remains of primary importance for detection of the emergence of antibiotic resistances to first-line drugs, and to test new therapeutic alternatives...
2017: Frontiers in Cellular and Infection Microbiology
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