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https://www.readbyqxmd.com/read/29167669/iron-induces-anti-tumor-activity-in-tumor-associated-macrophages
#1
Milene Costa da Silva, Michael O Breckwoldt, Francesca Vinchi, Margareta P Correia, Ana Stojanovic, Carl Maximilian Thielmann, Michael Meister, Thomas Muley, Arne Warth, Michael Platten, Matthias W Hentze, Adelheid Cerwenka, Martina U Muckenthaler
Tumor-associated macrophages (TAMs) frequently help to sustain tumor growth and mediate immune suppression in the tumor microenvironment (TME). Here, we identified a subset of iron-loaded, pro-inflammatory TAMs localized in hemorrhagic areas of the TME. The occurrence of iron-loaded TAMs (iTAMs) correlated with reduced tumor size in patients with non-small cell lung cancer. Ex vivo experiments established that TAMs exposed to hemolytic red blood cells (RBCs) were converted into pro-inflammatory macrophages capable of directly killing tumor cells...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29122658/endothelium-derived-contraction-in-a-model-of-rheumatoid-arthritis-is-mediated-via-angiotensin-ii-type-1-receptors
#2
Kayleigh Hamilton, Lynette Dunning, William R Ferrell, John C Lockhart, Andrew MacKenzie
A role for endothelium-derived constricting factors (EDCF), and the angiotensin II type 1 receptor (AT1R) pathway, in the vascular impairment found in the rat Freund's complete adjuvant (FCA)-model of rheumatoid arthritis (RA) was examined. FCA arthritis was induced in rats±losartan. Vehicle-treated rats served as controls. Knee-joint swelling and red blood cell (RBC) aggregation were measured as indicators of inflammation and endothelium reactivity assessed by response to acetylcholine (ACh) on aortic rings...
November 6, 2017: Vascular Pharmacology
https://www.readbyqxmd.com/read/29111410/the-z-spectrum-from-human-blood-at-7t
#3
Simon M Shah, Olivier E Mougin, Andrew J Carradus, Nicolas Geades, Richard Dury, William Morley, Penny A Gowland
Chemical Exchange Saturation Transfer (CEST) has been used to assess healthy and pathological tissue in both animals and humans. However, the CEST signal from blood has not been fully assessed. This paper presents the CEST and nuclear Overhauser enhancement (NOE) signals detected in human blood measured via z-spectrum analysis. We assessed the effects of blood oxygenation levels, haematocrit, cell structure and pH upon the z-spectrum in ex vivo human blood for different saturation powers at 7T. The data were analysed using Lorentzian difference (LD) model fitting and AREX (to compensate for changes in T1), which have been successfully used to study CEST effects in vivo...
October 27, 2017: NeuroImage
https://www.readbyqxmd.com/read/29107162/artificial-stroke-clots-how-wide-is-the-gap-to-the-real-world
#4
Maria Berndt, Sascha Prothmann, Christian Maegerlein, Paul Oberdieck, Claus Zimmer, Barbara Hegge, Jaroslav Pelisek, Lucas Schirmer, Holger Poppert, Tobias Boeckh-Behrens
OBJECTIVE: Especially since the establishment of mechanical thrombectomy as part of the standard stroke therapy, artificial thrombi have become important in the training of interventionalists as well as for the development and testing of devices. So far, these in vitro clots lack direct comparisons with ex vivo thrombi. We therefore compared the histological appearance of dynamically produced clots with that of stroke thrombi acquired during mechanical recanalization. METHODS: Thrombi of 145 consecutive stroke patients with large-vessel occlusions were histologically compared with 10 artificial clots, dynamically created from human blood and pig's blood using a Chandler loop system...
October 26, 2017: World Neurosurgery
https://www.readbyqxmd.com/read/29103845/negative-pressure-ventilation-decreases-inflammation-and-lung-edema-during-normothermic-ex-vivo-lung-perfusion
#5
Nader S Aboelnazar, Sayed Himmat, Sanaz Hatami, Christopher W White, Mohamad S Burhani, Peter Dromparis, Nobutoshi Matsumura, Ganghong Tian, Jason R B Dyck, Michael Mengel, Darren H Freed, Jayan Nagendran
BACKGROUND: Normothermic ex-vivo lung perfusion (EVLP) using positive pressure ventilation (PPV) and both acellular and red blood cell (RBC)-based perfusate solutions have increased the rate of donor organ utilization. We sought to determine whether a negative pressure ventilation (NPV) strategy would improve donor lung assessment during EVLP. METHODS: Thirty-two pig lungs were perfused ex vivo for 12 hours in a normothermic state, and were allocated equally to 4 groups according to the mode of ventilation (positive pressure ventilation [PPV] vs NPV) and perfusate composition (acellular vs RBC)...
September 14, 2017: Journal of Heart and Lung Transplantation
https://www.readbyqxmd.com/read/29101126/induction-of-deubiquitinating-enzyme-usp50-during-erythropoiesis-and-its-potential-role-in-the-regulation-of-ku70-stability
#6
Junting Cai, Jianxin Wei, Valerie Schrott, Jing Zhao, Grant Bullock, Yutong Zhao
Anemia is a very common blood disorder that affects the lives of billions of people worldwide. Anemia is caused by the loss of blood, increased destruction of red blood cells (RBCs), or reduced production of RBCs. Erythropoiesis is the complex process of RBC differentiation and maturation, in which protein degradation plays a crucial role. Protein ubiquitination regulates programmed protein degradation, which can be reversed by deubiquitinating enzymes (DUBs); however, the role of DUBs in erythropoiesis has not been well studied...
November 3, 2017: Journal of Investigative Medicine: the Official Publication of the American Federation for Clinical Research
https://www.readbyqxmd.com/read/29074889/unravelling-pathways-downstream-sox6-induction-in-k562-erythroid-cells-by-proteomic-analysis
#7
Gloria Barbarani, Antonella Ronchi, Margherita Ruoppolo, Lucia Santorelli, Robert Steinfelder, Sudharshan Elangovan, Cristina Fugazza, Marianna Caterino
The Sox6 transcription factor is crucial for terminal maturation of definitive red blood cells. Sox6-null mouse fetuses present misshapen and nucleated erythrocytes, due to impaired actin assembly and cytoskeleton stability. These defects are accompanied with a reduced survival of Sox6(-/-) red blood cells, resulting in a compensated anemia. Sox6-overexpression in K562 cells and in human primary ex vivo erythroid cultures enhances erythroid differentiation and leads to hemoglobinization, the hallmark of erythroid maturation...
October 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29074349/structure-optimization-of-tetrahydropyridoindole-based-aldose-reductase-inhibitors-improved-their-efficacy-and-selectivity
#8
Magdalena Majekova, Jana Ballekova, Marta Prnova, Milan Stefek
In our previous study, tetrahydropyridoindoles carboxymethylated in position 8 were identified as aldose reductase (ALR2) inhibitors with mild efficacy and selectivity yet with significant antioxidant activity. In the present study we proceeded with optimization of the tetrahydropyridoindole scaffold by shifting the carboxymethyl pharmacophore from position 8 to position 5, with the aim to improve the biological activity. Commercial databases were screened for the presence of tetrahydropyridoindoles carboxymethylated in position 5 and an experimental set of eight compounds was created...
October 16, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/29049291/a-deep-convolutional-neural-network-for-classification-of-red-blood-cells-in-sickle-cell-anemia
#9
Mengjia Xu, Dimitrios P Papageorgiou, Sabia Z Abidi, Ming Dao, Hong Zhao, George Em Karniadakis
Sickle cell disease (SCD) is a hematological disorder leading to blood vessel occlusion accompanied by painful episodes and even death. Red blood cells (RBCs) of SCD patients have diverse shapes that reveal important biomechanical and bio-rheological characteristics, e.g. their density, fragility, adhesive properties, etc. Hence, having an objective and effective way of RBC shape quantification and classification will lead to better insights and eventual better prognosis of the disease. To this end, we have developed an automated, high-throughput, ex-vivo RBC shape classification framework that consists of three stages...
October 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/29032941/ferritin-iron-regulators-pcbp1-and-ncoa4-respond-to-cellular-iron-status-in-developing-red-cells
#10
Moon-Suhn Ryu, Kari A Duck, Caroline C Philpott
Developing red blood cells exhibit multiple, redundant systems for regulating and coordinating the uptake of iron, the synthesis of heme, and the formation of hemoglobin during terminal differentiation. We recently described the roles of poly rC-binding protein (PCBP1) and nuclear coactivator 4 (NCOA4) in mediating the flux of iron through ferritin in developing erythroid cells, with PCBP1, an iron chaperone, delivering iron to ferritin and NCOA4, an autophagic cargo receptor, directing ferritin to the lysosome for degradation and iron release...
September 28, 2017: Blood Cells, Molecules & Diseases
https://www.readbyqxmd.com/read/28940437/analysis-of-argonaute-2-microrna-complexes-in-ex-vivo-stored-red-blood-cells
#11
Long Vu, Viswanath Ragupathy, Sandhya Kulkarni, Chintamani Atreya
BACKGROUND: Human enucleated mature red blood cells (RBCs) contain both mature microRNAs (miRNAs) and mRNAs, and we have previously correlated RBC storage lesion processes such as eryptosis, adenosine 5'-triphosphate loss, and RBC indices with differentially expressed miRNAs. Here we have characterized Argonaute 2 (AGO2)-miRNA complexes in stored mature RBCs as a first step toward understanding their role, if any. STUDY DESIGN AND METHODS: In this report AGO2-bound miRNAs in mature RBCs isolated from RBCs collected from three different healthy donors and stored for 24 hours at 4 to 6°C were identified by anti-AGO2 immunoprecipitation (IP) followed by next-generation sequencing of the RNA isolated from the IP...
September 20, 2017: Transfusion
https://www.readbyqxmd.com/read/28911146/anemia-in-patients-with-resistance-to-thyroid-hormone-%C3%AE-a-role-for-thyroid-hormone-receptor-%C3%AE-in-human-erythropoiesis
#12
COMPARATIVE STUDY
Anja L M van Gucht, Marcel E Meima, Carla Moran, Maura Agostini, Anna Tylki-Szymanska, Malgorzata-Walasek Krajewska, Krystyna Chrzanowska, Alexandra Efthymiadou, Dionisios Chrysis, Korcan Demir, W Edward Visser, Theo J Visser, Krishna Chatterjee, Thamar B van Dijk, Robin P Peeters
Context: Patients with resistance to thyroid hormone (TH) α (RTHα) are characterized by growth retardation, macrocephaly, constipation, and abnormal thyroid function tests. In addition, almost all RTHα patients have mild anemia, the pathogenesis of which is unknown. Animal studies suggest an important role for TH and TH receptor (TR)α in erythropoiesis. Objective: To investigate whether a defect in TRα affects the maturation of red blood cells in RTHα patients...
September 1, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28871825/the-effects-of-ex-vivo-ozone-treatment-on-human-erythrocyte-carbonic-anhydrase-enzyme
#13
Gülten Erken, Haydar Ali Erken, Cigdem Bilen, Nahit Gencer
Ozone autohemotherapy is used in the treatment of some diseases. Carbonic anhydrases (CAs, EC 4.2.1.1) are metalloenzymes and play a role in homeostatic mechanisms. The aim of this study was to investigate the effects of ozone on human red blood cell CA (hCA) enzyme activity. Blood samples were treated with different doses of ozone (10, 20, 30 µg/ml) and the erythrocyte total CA activities were determined. Also, purified hCAI and hCAII isozymes were treated with the same doses of ozone and the enzyme activities were measured...
September 5, 2017: Archives of Physiology and Biochemistry
https://www.readbyqxmd.com/read/28855161/possible-roles-for-atp-release-from-rbcs-exclude-the-camp-mediated-panx1-pathway
#14
Alex S Keller, Lukas Diederich, Christina Panknin, Leon J DeLalio, Joshua C Drake, Robyn Sherman, Edwin Kerry Jackson, Zhen Yan, Malte Kelm, Miriam M Cortese-Krott, Brant E Isakson
Red blood cell (RBC)-derived adenosine triphosphate (ATP) has been proposed as an integral component in the regulation of oxygen supply to skeletal muscle. In ex vivo settings RBCs have been shown to release ATP in response to a number of stimuli, including stimulation of adrenergic receptors. Further evidence suggested that ATP release from RBCs was dependent on activation of adenylate cyclase (AC)/ cyclic adenosine monophosphate (cAMP)-dependent pathways and involved the Pannexin 1 (Panx1) channel. Here we show that RBCs express Panx1, and confirm its absence in Panx1 knockout ((-/-)) RBCs...
August 30, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28838463/beware-cold-agglutinins-in-organ-donors-ex%C3%A2-vivo-lung-perfusion-from-an-uncontrolled-donation-after-circulatory-determination-of-death-donor-with-a-cold-agglutinin-a-case-report
#15
A Venkataraman, J W Blackwell, W K Funkhouser, K R Birchard, S E Beamer, W T Simmons, S H Randell, T M Egan
BACKGROUND: We began to recover lungs from uncontrolled donation after circulatory determination of death to assess for transplant suitability by means of ex vivo lung perfusion (EVLP) and computerized tomographic (CT) scan. Our first case had a cold agglutinin with an interesting outcome. CASE REPORT: A 60-year-old man collapsed at home and was pronounced dead by Emergency Medical Services personnel. Next-of-kin consented to lung retrieval, and the decedent was ventilated and transported...
September 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28780446/biochemical-responses-to-cadmium-exposure-in-oncorhynchus-mykiss-erythrocytes
#16
Patrick Orlando, Sonia Silvestri, Enea Ferlizza, Giulia Andreani, Emilio Carpenè, Giancarlo Falcioni, Luca Tiano, Gloria Isani
Cd is known for its carcinogenic effects, however its mechanism of toxicity and in particular its ability to promote oxidative stress is debated. In fact, although it is considered a redox-inactive metal, at high concentration Cd was shown to promote indirectly oxidative stress. In this study we investigated metal accumulation in ex vivo exposed trout (Oncorhynchus mykiss) erythrocytes and Cd dose-dependent effect in terms of RBC viability, cytosolic and mitochondrial ROS levels as well as its effects on mitochondrial membrane depolarization, hemoglobin stability and precipitation...
August 3, 2017: Ecotoxicology and Environmental Safety
https://www.readbyqxmd.com/read/28774826/erythrocyte-based-drug-delivery-in-transfusion-medicine-wandering-questions-seeking-answers
#17
REVIEW
Vassilis L Tzounakas, Dimitrios G Karadimas, Issidora S Papassideri, Jerard Seghatchian, Marianna H Antonelou
Red blood cells (RBCs) represent the most commonly used and best-studied natural carriers in the history of drug delivery. Their abundance and long circulation half-life, their great immune-biocompatibility and biodegradability profiles, along with the availability of well established protocols for their safe collection, ex vivo processing and quality control make them advantageous as drug delivery systems (DDS). As a result, several drug-loading techniques (including encapsulation and surface conjugation) have been developed in order to construct RBC-based or RBC-inspired drug delivery vehicles for the effective treatment of infections, cancer, chronic and autoimmune diseases in both pre-clinical protocols and clinical trials...
July 16, 2017: Transfusion and Apheresis Science
https://www.readbyqxmd.com/read/28760888/ag-348-enhances-pyruvate-kinase-activity-in-red-blood-cells-from-patients-with-pyruvate-kinase-deficiency
#18
Charles Kung, Jeff Hixon, Penelope A Kosinski, Giovanni Cianchetta, Gavin Histen, Yue Chen, Collin Hill, Stefan Gross, Yaguang Si, Kendall Johnson, Byron DeLaBarre, Zhiyong Luo, Zhiwei Gu, Gui Yao, Huachun Tang, Cheng Fang, Yingxia Xu, Xiaobing Lv, Scott Biller, Shin-San Michael Su, Hua Yang, Janeta Popovici-Muller, Francesco Salituro, Lee Silverman, Lenny Dang
Pyruvate kinase (PK) deficiency is a rare genetic disease that causes chronic hemolytic anemia. There are currently no targeted therapies for PK deficiency. Here, we describe the identification and characterization of AG-348, an allosteric activator of PK that is currently in clinical trials for the treatment of PK deficiency. We demonstrate that AG-348 can increase the activity of wild-type and mutant PK enzymes in biochemical assays and in patient red blood cells treated ex vivo. These data illustrate the potential for AG-348 to restore the glycolytic pathway activity in patients with PK deficiency and ultimately lead to clinical benefit...
September 14, 2017: Blood
https://www.readbyqxmd.com/read/28755871/cyclohexene-fused-1-3-oxazines-with-selective-antibacterial-and-antiparasitic-action-and-low-cytotoxic-effects
#19
Maria R M de Brito, Walter J Peláez, Martín S Faillace, Gardenia C G Militão, Jackson R G S Almeida, Gustavo A Argüello, Zsolt Szakonyi, Ferenc Fülöp, Maria C Salvadori, Fernanda S Teixeira, Rivelilson M Freitas, Pedro L S Pinto, Ana C Mengarda, Marcos P N Silva, Ademar A Da Silva Filho, Josué de Moraes
Oxazine derivatives, a class of heterocyclic compounds, exhibit a variety of biological properties, such as anticonvulsant and antitumor activities. In this study, we evaluated the effect of two cyclohexene-fused 1,3-oxazines (cis‑1-benzyl-N-phenyl-1,4,4a,5,8,8a-hexahydro-3,1-benzoxazin-2-imine (1) and trans‑N-phenyl-1,4,4a,5,8,8a-hexahydro-3,1-benzoxazin-2-imine (2)) in cultures of Bacillus cereus, Enterococcus faecalis, Escherichia coli, Klebsiella pneumoniae, Salmonella enterica, Serratia marcescens, Shigella flexneri and Staphylococcus aureus by the Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC)...
October 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28741656/biochemical-evaluation-of-storage-lesion-in-canine-packed-erythrocytes
#20
C R Wilson, M B Pashmakova, J A Heinz, M C Johnson, H M Minard, M A Bishop, J W Barr
OBJECTIVES: This study describes the biochemical changes - also known as the storage lesion - that occur in canine packed red blood cells during ex vivo storage. MATERIALS AND METHODS: Ten 125-mL units of non-leuco-reduced packed red blood cells in citrate phosphate dextrose adenine were obtained from a commercial blood bank within 24 hours of donation. Samples were aseptically collected on days 1, 4, 7, 14, 28, 35 and 42 for measurement of sodium, potassium, chloride, lactate, glucose, pH and ammonia concentrations...
July 25, 2017: Journal of Small Animal Practice
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