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https://www.readbyqxmd.com/read/28438069/emerging-graft-protective-strategies-in-clinical-liver-transplantation
#1
Arash Nickkholgh, Daniel Maluf
There have been remarkable efforts to characterize the key responsible pathophysiologic mechanisms, as well as to ameliorate the organ preservation and ischemia reperfusion injury with the ultimate goal of expanding the donor pool and further improvement of the outcomes of the liver transplantation. Attempts to translate the experimental results from bench to bedside have yielded no valid protective concepts in the field of clinical liver transplantation yet. Nonetheless, there has been a considerable amount of ongoing clinical research to develop clinically relevant graft protective strategies...
April 24, 2017: Expert Review of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28428348/predictors-of-the-aspiration-component-success-of-a-direct-aspiration-first-pass-technique-adapt-for-the-endovascular-treatment-of-stroke-reperfusion-strategy-in-anterior-circulation-acute-stroke
#2
Raphaël Blanc, Hocine Redjem, Gabriele Ciccio, Stanislas Smajda, Jean-Philippes Desilles, Eliane Orng, Guillaume Taylor, Elodie Drumez, Robert Fahed, Julien Labreuche, Mikael Mazighi, Bertrand Lapergue, Michel Piotin
BACKGROUND AND PURPOSE: The technique of a direct aspiration first pass technique (ADAPT) for the endovascular treatment of stroke has been reported to be fast, safe, and effective for the treatment of acute ischemic stroke. The aim of this study is to determine the preoperative factors that affect success of the aspiration component of the technique in ischemic stroke patients with large vessel occlusion in the anterior circulation. METHODS: We enrolled all 347 consecutive patients with anterior circulation acute ischemic stroke admitted for mechanical thrombectomy at our institution from August 2013 to October 2015 and treated by ADAPT for the endovascular treatment of stroke...
April 20, 2017: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/28426808/a-screen-for-protective-drugs-against-delayed-hypoxic-injury
#3
Chun-Ling Sun, Huiliang Zhang, Meng Liu, Wang Wang, C Michael Crowder
Despite longstanding efforts to develop cytoprotective drugs against ischemia/reperfusion (IR) injuries, there remains no effective therapeutics to treat hypoxic injury. The failure of traditional strategies at solving this problem suggests the need for novel and unbiased approaches that can lead to previously unsuspected targets and lead compounds. Towards this end, we report here a unique small molecule screen in the nematode C. elegans for compounds that improve recovery when applied after the hypoxic insult, using a C...
2017: PloS One
https://www.readbyqxmd.com/read/28421173/cerebral-autoregulation-brain-injury-and-the-transitioning-premature-infant
#4
REVIEW
Zachary A Vesoulis, Amit M Mathur
Improvements in clinical management of the preterm infant have reduced the rates of the two most common forms of brain injury, such as severe intraventricular hemorrhage and white matter injury, both of which are contributory factors in the development of cerebral palsy. Nonetheless, they remain a persistent challenge and are associated with a significant increase in the risk of adverse neurodevelopment outcomes. Repeated episodes of ischemia-reperfusion represent a common pathway for both forms of injury, arising from discordance between systemic blood flow and the innate regulation of cerebral blood flow in the germinal matrix and periventricular white matter...
2017: Frontiers in Pediatrics
https://www.readbyqxmd.com/read/28420961/the-role-of-astrocytes-in-neuroprotection-after-brain-stroke-potential-in-cell-therapy
#5
REVIEW
Andrea Becerra-Calixto, Gloria P Cardona-Gómez
Astrocytes are commonly involved in negative responses through their hyperreactivity and glial scar formation in excitotoxic and/or mechanical injuries. But, astrocytes are also specialized glial cells of the nervous system that perform multiple homeostatic functions for the survival and maintenance of the neurovascular unit. Astrocytes have neuroprotective, angiogenic, immunomodulatory, neurogenic, and antioxidant properties and modulate synaptic function. This makes them excellent candidates as a source of neuroprotection and neurorestoration in tissues affected by ischemia/reperfusion, when some of their deregulated genes can be controlled...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28416795/neutrophil-stunning-by-metoprolol-reduces-infarct-size
#6
Jaime García-Prieto, Rocío Villena-Gutiérrez, Mónica Gómez, Esther Bernardo, Andrés Pun-García, Inés García-Lunar, Georgiana Crainiciuc, Rodrigo Fernández-Jiménez, Vinatha Sreeramkumar, Rafael Bourio-Martínez, José M García-Ruiz, Alfonso Serrano Del Valle, David Sanz-Rosa, Gonzalo Pizarro, Antonio Fernández-Ortiz, Andrés Hidalgo, Valentín Fuster, Borja Ibanez
The β1-adrenergic-receptor (ADRB1) antagonist metoprolol reduces infarct size in acute myocardial infarction (AMI) patients. The prevailing view has been that metoprolol acts mainly on cardiomyocytes. Here, we demonstrate that metoprolol reduces reperfusion injury by targeting the haematopoietic compartment. Metoprolol inhibits neutrophil migration in an ADRB1-dependent manner. Metoprolol acts during early phases of neutrophil recruitment by impairing structural and functional rearrangements needed for productive engagement of circulating platelets, resulting in erratic intravascular dynamics and blunted inflammation...
April 18, 2017: Nature Communications
https://www.readbyqxmd.com/read/28414974/bilirubin-nanoparticle-preconditioning-protects-against-hepatic-ischemia-reperfusion-injury
#7
Jin Yong Kim, Dong Yun Lee, Sukmo Kang, Wenjun Miao, Hyungjun Kim, Yonghyun Lee, Sangyong Jon
Hepatic ischemia-reperfusion injury (IRI) remains a major concern in liver transplantation and resection, despite continuing efforts to prevent it. Accumulating evidence suggests that bilirubin possesses antioxidant, anti-inflammatory and anti-apoptotic properties. However, despite obvious potential health benefits of bilirubin, its clinical applications are limited by its poor solubility. We recently developed bilirubin nanoparticles (BRNPs) consisting of polyethylene glycol (PEG)-conjugated bilirubin. Here, we sought to investigate whether BRNPs protect against IRI in the liver by preventing oxidative stress...
April 12, 2017: Biomaterials
https://www.readbyqxmd.com/read/28412905/therapeutic-potential-of-heme-oxygenase-1-carbon-monoxide-system-against-ischemia-reperfusion-injury
#8
Yuanyuan Cheng, Jianhui Rong
BACKGROUND: Ischemia-reperfusion (I/R) injury causes the dysfunctions of different major organs, leading to morbidity and mortality on the global scale. Among a battery of therapeutic targets, the heme oxygenase-1 (HO-1)/carbon monoxide (CO) system has been evaluated for the development of new therapies against I/R injury. The enzyme HO-1 catalyzes the degradation of heme into three biologically active end products, namely biliverdin/bilirubin, CO and ferrous ion. Interestingly, CO is one of a few bioactive gaseous molecules with the capability of regulating inflammation, cell survival and growth...
April 13, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28407626/exogenous-mirna-146a-enhances-the-therapeutic-efficacy-of-human-mesenchymal-stem-cells-by-increasing-vascular-endothelial-growth-factor-secretion-in-the-ischemia-reperfusion-injured-heart
#9
Hyang-Hee Seo, Se-Yeon Lee, Chang Youn Lee, Ran Kim, Pilseog Kim, Sekyung Oh, Hojin Lee, Min Young Lee, Jongmin Kim, Lark Kyun Kim, Ki-Chul Hwang, Woochul Chang
Adult stem cells have been studied as a promising therapeutic modality for the functional restoration of the damaged heart. In the present study, a strategy for enhancing the angiogenic efficacy of human mesenchymal stem cells (hMSCs) using micro-RNA was examined. We investigated whether micro-RNA-146a (miR-146a) influences the secretion of vascular endothelial growth factor (VEGF) and angiogenesis of MSCs. Our data indicated that miR-146a-transfected hMSCs (hMSCmiR-146a) decreased the expression of neurofibromin 2, an inhibitor of p21-activated kinase-1 (PAK1)...
April 14, 2017: Journal of Vascular Research
https://www.readbyqxmd.com/read/28403647/parathyroid-hormone-related-peptide-a-novel-endocrine-cardioprotective-conditioning-mimetic
#10
Tanuka Datta, Karin Przyklenk, Nabanita S Datta
An as-yet limited body of evidence suggests that calcium-regulating endocrine hormones-in particular, parathyroid hormone-related peptide (PTHrP)-may have unappreciated cardioprotective effects. The current review focuses on the concept that PTHrP may, via modulation of classic cardioprotective signaling pathways, provide a novel strategy to attenuate myocardial ischemia-reperfusion injury.
January 1, 2017: Journal of Cardiovascular Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28398674/melatonin-protects-cardiac-microvasculature-against-ischemia-reperfusion-injury-via-suppression-of-mitochondrial-fission-vdac1-hk2-mptp-mitophagy-axis
#11
Hao Zhou, Ying Zhang, Shunying Hu, Chen Shi, Pingjun Zhu, Qiang Ma, Qinhua Jin, Feng Cao, Feng Tian, Yundai Chen
The cardiac microvascular system, which is primarily composed of monolayer endothelial cells, is the site of blood supply and nutrient exchange to cardiomyocytes. However, microvascular ischemia/reperfusion injury (IRI) following percutaneous coronary intervention is a woefully neglected topic and few strategies are available to reverse such pathologies. Here, we studied the effects of melatonin on microcirculation IRI and elucidated the underlying mechanism. Melatonin markedly reduced infarcted area, improved cardiac function, restored blood flow and lower microcirculation perfusion defects...
April 11, 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/28397127/a-novel-strategy-to-enhance-angiogenesis-in-vivo-using-the-small-vegf-binding-peptide-pr1p
#12
Avner Adini, Irit Adini, Zai-Long Chi, Ratmir Derda, Amy E Birsner, Benjamin D Matthews, Robert J D'Amato
Therapeutic angiogenesis is an experimental frontier in vascular biology that seeks to deliver angiogenic growth factors to ischemic or injured tissues to promote targeted formation of new blood vessels as an alternative approach to surgical revascularization procedures. Vascular endothelial growth factor (VEGF) is a potent angiogenic signal protein that is locally upregulated at sites of tissue injury. However, therapies aimed at increasing VEGF levels experimentally by injecting VEGF gene or protein failed to improve outcomes in human trials in part due to its short half-life and systemic toxicity...
April 10, 2017: Angiogenesis
https://www.readbyqxmd.com/read/28391169/hypoxia-induced-extracellular-vesicles-mediate-protection-of-remote-ischemic-preconditioning-for-renal-ischemia-reperfusion-injury
#13
Guangyuan Zhang, Yu Yang, Yeqing Huang, Lei Zhang, Zhixin Ling, Yingjian Zhu, Feng Wang, Xiangyu Zou, Ming Chen
Remote ischemic preconditioning (rIPC) is a reliable strategy for prevention of injury to various organs. However the mechanism by which it does so is still unclear. In the present study, serum and EVs isolated from ischemic preconditioned right renal venous perfusates were injected into rats with ischemia-reperfusion-injured kidneys immediately after reperfusion. The animals were killed 24h later. Tubular scores and renal function were tested to evaluate the therapeutic effects. To further explore the underlying mechanism, HK-2 cells derived EVs under hypoxia were also administrated to rats with left kidney IRI...
April 6, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28389361/annexin-a1-nuclear-translocation-induces-retinal-ganglion-cell-apoptosis-after-ischemia-reperfusion-injury-through-the-p65-il-1%C3%AE-pathway
#14
Yin Zhao, Xing Li, Jieling Gong, Lu Li, Liwen Chen, Lu Zheng, Zhiqi Chen, Jing Shi, Hong Zhang
The degeneration of retinal ganglion cells (RGCs) has been identified as a major problem in glaucoma. Previous studies have indicated an association between annexin A1 (ANXA1) and neuronal cell apoptosis, and RGCs apoptosis in acute ischemia-reperfusion was attributed to an increased production of IL-1β. We found that the expression and nuclear translocation of ANXA1 were upregulated in models of acute ischemia-reperfusion in RGCs in vivo. ANXA1 was found to have a promoting effect on the expression of IL-1β in primary cultured RGCs, which could be inhibited by treatment with ANXA1 shRNA or the p65 inhibitor BAY 11-7082...
April 4, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28386847/inhibition-of-intracellular-type-10-adenylyl-cyclase-protects-cortical-neurons-against-reperfusion-induced-mitochondrial-injury-and-apoptosis
#15
Megha Chagtoo, Nelson George, Neelam Pathak, Swasti Tiwari, Madan M Godbole, Yury Ladilov
Mitochondrial injury significantly contributes to the neuronal death under cerebral ischemia and reperfusion. Within several signaling pathways, cyclic adenosine monophosphate (cAMP) signaling plays a substantial role in mitochondrial injury and cell death. Traditionally, the source of cellular cAMP has been attributed to the membrane-bound adenylyl cyclase, whereas the role of the intracellular localized type 10 soluble adenylyl cyclase (sAC) in neuronal pathology has not been considered. Since neurons express an active form of sAC, we aimed to investigate the role of sAC in reperfusion-induced neuronal apoptosis...
April 6, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28382073/at1-receptor-modulator-attenuates-the-hypercholesterolemia-induced-impairment-of-the-myocardial-ischemic-post-conditioning-benefits
#16
Yun-Wei Li, Yan-Ming Li, Yan Hon, Qi-Lin Wan, Rui-Li He, Zhi-Zhong Wang, Cui-Hua Zhao
BACKGROUND AND OBJECTIVES: Ischemic post-conditioning (PostC) has been demonstrated as a novel strategy to harness nature's protection against myocardial ischemia-reperfusion (I/R). Hypercholesterolemia (HC) has been reported to block the effect of PostC on the heart. Angiotensin II type-1 (AT1) modulators have shown benefits in myocardial ischemia. The present study investigates the effect of a novel inhibitor of AT1, azilsartan in PostC of the heart of normocholesterolemic (NC) and HC rats...
March 2017: Korean Circulation Journal
https://www.readbyqxmd.com/read/28381122/argon-exposure-induces-postconditioning-in-myocardial-ischemia-reperfusion
#17
Sandrine Lemoine, Katrien Blanchart, Mathieu Souplis, Adrien Lemaitre, Damien Legallois, Laurent Coulbault, Christophe Simard, Stéphane Allouche, Jacques H Abraini, Jean-Luc Hanouz, René Rouet, Laurent Sallé, Romain Guinamard, Alain Manrique
BACKGROUND AND PURPOSE: Cardioprotection against ischemia-reperfusion (I/R) damages remains a major concern during prehospital management of acute myocardial infarction. Noble gases have shown beneficial effects in preconditioning studies. Because emergency proceedings in the context of myocardial infarction require postconditioning strategies, we evaluated the effects of argon in such protocols on mammalian cardiac tissue. EXPERIMENTAL APPROACHES: In rat, cardiac I/R was induced in vivo by transient coronary artery ligature and cardiac functions were evaluated by magnetic resonance imaging...
January 1, 2017: Journal of Cardiovascular Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28381115/remote-ischemic-conditioning-for-patients-with-stemi
#18
Michael Rahbek Schmidt, Mathis Ersted Rasmussen, Hans Erik Bøtker
ST-segment elevation myocardial infarction (STEMI) remains a leading cause of death and morbidity, despite declining incidence and improved short-term outcome in many countries. Although mortality declines in developed countries with easy and fast access to optimized treatment, development of heart failure often remains a challenge in survivors and still approaches 10% at 1 year. Rapid admission and acute interventional treatment combined with modern antithrombotic pharmacologic therapy frequently establish complete reperfusion and acutely stabilize the patient, but the reperfusion itself adds further to the damage in the myocardium compromising the long-term outcome...
January 1, 2017: Journal of Cardiovascular Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28379489/new-thrombolytic-strategy-providing-neuroprotection-in-experimental-ischemic-stroke-mmp10-alone-or-in-combination-with-tpa
#19
C Roncal, S Martinez de Lizarrondo, A Salicio, A Chevilley, J A Rodriguez, A Rosell, P O Couraud, B Weksler, J Montaner, D Vivien, J A Páramo, J Orbe
Aim: Considering that MMP-10 improves stroke injury, we have examined the therapeutic and protective effect of MMP10 and tPA/MMP10 as clot-dissolving and neuroprotective agent in an experimental model of ischemic stroke and studied in vitro the molecular pathways involved in MMP10-mediated effects. Methods and Results: Cerebral ischemia was induced by the local injection of thrombin into the middle cerebral artery followed by reperfusion with MMP10 (6.5µg/Kg) and tPA (10mg/Kg) alone or in combination with MMP10...
April 3, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28378915/structure-of-6-diazo-5-oxo-norleucine-bound-human-gamma-glutamyl-transpeptidase-1-a-novel-mechanism-of-inactivation
#20
Simon S Terzyan, Paul F Cook, Annie Heroux, Marie H Hanigan
Intense efforts are underway to identify inhibitors of the enzyme gamma-glutamyl transpeptidase 1 (GGT1) which cleaves extracellular gamma-glutamyl compounds and contributes to the pathology of asthma, reperfusion injury and cancer. The glutamate analog, 6-diazo-5-oxo-norleucine (DON), inhibits GGT1. DON also inhibits many essential glutamine metabolizing enzymes rendering it too toxic for use in the clinic as a GGT1 inhibitor. We investigated the molecular mechanism of human GGT1 (hGGT1) inhibition by DON to determine possible strategies for increasing its specificity for hGGT1...
April 5, 2017: Protein Science: a Publication of the Protein Society
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