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https://www.readbyqxmd.com/read/28730969/the-battle-for-iron-between-humans-and-microbes
#1
Peggy L Carver
Iron is an essential micronutrient for bacteria, fungi, and humans; as such, each has evolved specialized iron uptake systems to acquire iron from the extracellular environment and a complex 'tug of war' has evolved between human hosts and pathogenic microorganisms in the battle for this vital nutrient. In humans, sequestration (hiding) of iron from invading pathogens is often successful; however, many pathogens have evolved mechanisms to circumvent this approach. Clinically, controversy continues whether iron overload or administration of iron results in an increased risk of infection...
July 20, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28729680/the-use-of-radiocobalt-as-a-label-improves-imaging-of-egfr-using-dota-conjugated-affibody-molecule
#2
Javad Garousi, Ken G Andersson, Johan H Dam, Birgitte B Olsen, Bogdan Mitran, Anna Orlova, Jos Buijs, Stefan Ståhl, John Löfblom, Helge Thisgaard, Vladimir Tolmachev
Several anti-cancer therapies target the epidermal growth factor receptor (EGFR). Radionuclide imaging of EGFR expression in tumours may aid in selection of optimal cancer therapy. The (111)In-labelled DOTA-conjugated ZEGFR:2377 Affibody molecule was successfully used for imaging of EGFR-expressing xenografts in mice. An optimal combination of radionuclide, chelator and targeting protein may further improve the contrast of radionuclide imaging. The aim of this study was to evaluate the targeting properties of radiocobalt-labelled DOTA-ZEGFR:2377...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28719386/is-there-a-standard-of-care-for-transfusion-therapy-in-thalassemia
#3
Massimo Franchini, Gian L Forni, Giancarlo M Liumbruno
PURPOSE OF REVIEW: Thalassemia is the most common form of inherited anemia, characterized by variable clinical phenotypes. The purpose of this review is to summarize the transfusion support in thalassemia patients and the management of transfusion-related iron overload. RECENT FINDINGS: The most recent evidence on transfusion strategy and iron chelation therapy in thalassemia arising from clinical trials as well as from recommendation guidelines are critically discussed...
July 14, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28708597/mri-based-evaluation-of-multiorgan-iron-overload-is-a-predictor-of-adverse-outcomes-in-pediatric-patients-undergoing-allogeneic-hematopoietic-stem-cell-transplantation
#4
Natalia Maximova, Massimo Gregori, Giulia Boz, Roberto Simeone, Davide Zanon, Giulia Schillani, Floriana Zennaro
The medical records of 44 pediatric patients who underwent allogeneic transplantation from 2011 to 2015 were retrospectively reviewed. Magnetic resonance imaging was used to measure iron concentrations in the liver, spleen, pancreas and bone. These patients were divided into two groups, 18 with non-elevated (< 100 μmol/g; Group 1) liver iron concentration before transplantation and 26 with elevated (> 100 μmol/g; Group 2) concentration . We compared transplant-related outcomes in the two groups. Iron overload was a negative prognostic risk factor for sinusoidal obstruction syndrome (OR = 17), osteoporosis (OR = 6...
July 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28707012/soluble-form-of-transferrin-receptor-1-level-is-associated-with-the-age-at-first-diagnosis-and-the-risk-of-therapeutic-intervention-and-iron-overloading-in-patients-with-non-transfusion-dependent-thalassemia
#5
Paolo Ricchi, Antonella Meloni, Silvia Costantini, Anna Spasiano, Tiziana Di Matola, Alessia Pepe, Patrizia Cinque, Aldo Filosa
We retrospectively evaluated the relationship between serum transferrin receptor-1 (sTfR1) and some fundamental events in the life and the management (the age at diagnosis, the age at the first red blood cells transfusion, the age at splenectomy, and the overall need of chelation therapy) of 111 patients with non-transfusion-dependent thalassemia (NTDT) subdivided in four genetic entities: patients with homozygous or compound heterozygous state for β-thalassemia, patients with triplicated α genotype associated with β heterozygosity, patients with deletional HbH, and patients with the combination of a β defect plus a β chain variant...
July 14, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28706555/advances-in-iron-chelation-therapy-transitioning-to-a-new-oral-formulation
#6
Nirmish R Shah
Iron overload is a concern for patients who require repeated red-blood-cell transfusions due to conditions such as sickle cell disease, thalassemia, or myelodysplastic syndromes. The recommended treatment for removing excess iron in these patients is iron chelation therapy. Currently available iron chelators include deferoxamine, which is administered by injection, and deferasirox and deferiprone, both of which are administered orally. Adherence to iron chelator therapy is an important consideration and may be affected by side effects...
2017: Drugs in Context
https://www.readbyqxmd.com/read/28705738/identification-of-novel-potential-scaffold-for-class-i-hdacs-inhibition-an-in-silico-protocol-based-on-virtual-screening-molecular-dynamics-mathematical-analysis-and-machine-learning
#7
Cong Fan, Yanxin Huang
Histone deacetylases (HDACs) family has been widely reported as an important class of enzyme targets for cancer therapy. Much effort has been made in discovery of novel scaffolds for HDACs inhibition besides existing hydroxamic acids, cyclic peptides, benzamides, and short-chain fatty acids. Herein we set up an in-silico protocol which not only could detect potential Zn(2+) chelation bonds but also still adopted non-bonded model to be effective in discovery of Class I HDACs inhibitors, with little human's subjective visual judgment involved...
July 10, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28704976/role-of-the-p-coumaroyl-moiety-in-the-antioxidant-and-cytoprotective-effects-of-flavonoid-glycosides-comparison-of-astragalin-and-tiliroside
#8
Xican Li, Yage Tian, Tingting Wang, Qiaoqi Lin, Xiaoyi Feng, Qian Jiang, Yamei Liu, Dongfeng Chen
The aim of this study was to explore the role of p-coumaroyl in the antioxidant and cytoprotective effects of flavonoid glycosides. The antioxidant effects of astragalin and tiliroside were compared using ferric ion reducing antioxidant power, DPPH• scavenging, ABTS•⁺ scavenging, •O₂(-) scavenging, and Fe(2+)-chelating assays. The results of these assays revealed that astragalin and tiliroside both exhibited dose-dependent activities; however, tiliroside exhibited lower IC50 values than astragalin...
July 12, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28703340/core-satellite-polydopamine-gadolinium-metallofullerene-nanotheranostics-for-multimodal-imaging-guided-combination-cancer-therapy
#9
Sheng Wang, Jing Lin, Zhantong Wang, Zijian Zhou, Ruiliang Bai, Nan Lu, Yijing Liu, Xiao Fu, Orit Jacobson, Wenpei Fan, Junle Qu, Siping Chen, Tianfu Wang, Peng Huang, Xiaoyuan Chen
Integration of magnetic resonance imaging (MRI) and other imaging modalities is promising to furnish complementary information for accurate cancer diagnosis and imaging-guided therapy. However, most gadolinium (Gd)-chelator MR contrast agents are limited by their relatively low relaxivity and high risk of released-Gd-ions-associated toxicity. Herein, a radionuclide-(64) Cu-labeled doxorubicin-loaded polydopamine (PDA)-gadolinium-metallofullerene core-satellite nanotheranostic agent (denoted as CDPGM) is developed for MR/photoacoustic (PA)/positron emission tomography (PET) multimodal imaging-guided combination cancer therapy...
July 13, 2017: Advanced Materials
https://www.readbyqxmd.com/read/28698780/liver-iron-content-lic-in-adults-with-sickle-cell-disease-scd-correlation-with-serum-ferritin-and-liver-enzymes-concentrations-in-trasfusion-dependent-td-scd-and-non-transfusion-dependent-nt-scd-patients
#10
Mohamed Yassin, Ashraf Soliman, Vincenzo De Sanctis, Abdelqadir Nashwan, Sandra Abusamaan, Abbas Moustafa, Samah Kohla, Dina Soliman
INTRODUCTION: Sickle cell disease (SCD) is one of the leading causes of morbidity and mortality worldwide, causing damage and dysfunction in multiple organs. The complications of this disease are numerous, affect every organ and/or tissue in the body and vary considerably among patients over the time challenging its management. THE AIM OF OUR STUDY: To determine the iron status of 17 patients with non-transfusion-dependent sickle cell disease ( NT-SCD) patients and six patients with transfusion dependent sickle cell disease (TD- SCD) using both serum ferritin level (SF) and Ferriscan® evaluation of liver iron content (LIC)...
2017: Mediterranean Journal of Hematology and Infectious Diseases
https://www.readbyqxmd.com/read/28695249/first-study-on-iron-complexes-in-blood-and-organ-samples-from-thalassaemic-and-normal-laboratory-mice-using-m%C3%A3-ssbauer-spectroscopy
#11
George Charitou, Vlassis Petousis, Charalambos Tsertos, Yannis Parpottas, Marina Kleanthous, Marios Phylactides, Soteroula Christou
Measurements of iron complexes and iron stores in the body are crucial for evaluation and management of chelation therapy targeted against iron accumulation or overload in blood and organs. In this work, blood and tissue samples from one normal and one thalassaemic laboratory mouse were studied using (57)Fe Mössbauer spectroscopy at 78 K for the first time. In contrast to human patients, these laboratory mice did not receive any medical treatment, thus the iron components present in the samples are not altered from their natural state...
July 10, 2017: European Biophysics Journal: EBJ
https://www.readbyqxmd.com/read/28692648/zebrafish-slc30a10-deficiency-revealed-a-novel-compensatory-mechanism-of-atp2c1-in-maintaining-manganese-homeostasis
#12
Zhidan Xia, Jiayu Wei, Yingniang Li, Jia Wang, Wenwen Li, Kai Wang, Xiaoli Hong, Lu Zhao, Caiyong Chen, Junxia Min, Fudi Wang
Recent studies found that mutations in the human SLC30A10 gene, which encodes a manganese (Mn) efflux transporter, are associated with hypermanganesemia with dystonia, polycythemia, and cirrhosis (HMDPC). However, the relationship between Mn metabolism and HMDPC is poorly understood, and no specific treatments are available for this disorder. Here, we generated two zebrafish slc30a10 mutant lines using the CRISPR/Cas9 system. Compared to wild-type animals, mutant adult animals developed significantly higher systemic Mn levels, and Mn accumulated in the brain and liver of mutant embryos in response to exogenous Mn...
July 10, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28690982/deferiprone-and-gallium-protoporphyrin-have-the-capacity-to-potentiate-the-activity-of-antibiotics-in-staphylococcus-aureus-small-colony-variants
#13
Katharina Richter, Nicky Thomas, Guimin Zhang, Clive A Prestidge, Tom Coenye, Peter-John Wormald, Sarah Vreugde
Small colony variants (SCVs) of bacteria like Staphylococcus aureus are characterized by a reduced colony size and are linked to increased antibiotic tolerance and resistance. Their altered expression of virulence factors, slow growing properties and their ability to form biofilms make the eradication of SCVs challenging. In the context of biofilm-related infectious diseases involving S. aureus SCVs, a therapy targeting bacterial iron metabolism was evaluated. The combination of the iron-chelator deferiprone (Def) and the heme-analog gallium-protoporphyrin (GaPP), in solution and incorporated in a surgical wound gel, was tested for activity against planktonic and sessile SCVs...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28689036/enhanced-vasculotoxic-metal-excretion-in-post-myocardial-infarction-patients-following-a-single-edetate-disodium-based-infusion
#14
Ivan A Arenas, Ana Navas-Acien, Ian Ergui, Gervasio A Lamas
Toxic metals have been associated with cardiovascular mortality and morbidity. We have hypothesized that enhanced excretion of vasculotoxic metals might explain the positive results of the Trial to Assess Chelation Therapy (TACT). The purpose of this study was to determine whether a single infusion of the edetate disodium- based infusion used in TACT led to enhanced excretion of toxic metals known to be associated with cardiovascular events. METHODS: Twenty six patients (post-MI, age > 50 years, serum creatinine ≤ 2...
July 6, 2017: Environmental Research
https://www.readbyqxmd.com/read/28687016/safety-and-tolerability-of-deferasirox-in-pediatric-hematopoietic-stem-cell-transplant-recipients-one-facility-s-five-years-experience-of-chelation-treatment
#15
Natalia Maximova, Massimo Gregori, Roberto Simeone, Aurelio Sonzogni, Giulia Boz, Carmen Fucile, Valeria Marini, Antonietta Martelli, Francesca Mattioli
42 pediatric patients with iron overload, who underwent liver biopsy and DFX treatment after hematopoietic stem cell transplantation were included in the study group. The patients were divided into two groups diversified according to deferasirox trough plasma concentrations (DFX Ctrough) with cut-off equal to10 mcg/mL. The average dose of DFX was 25.9 mg/kg in the DFX Ctrough < 10 mcg/mL group versus 19.2 mg/kg in the DFX Ctrough > 10 mcg/mL group (p=0,0003). The mean duration of DFX treatment was 135...
June 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28678794/ammonium-tetrathiomolybdate-following-ischemia-reperfusion-injury-chemistry-pharmacology-and-impact-of-a-new-class-of-sulfide-donor-in-preclinical-injury-models
#16
Alex Dyson, Felipe Dal-Pizzol, Giovanni Sabbatini, Anna B Lach, Federica Galfo, Juliano Dos Santos Cardoso, Bruna Pescador Mendonça, Iain Hargreaves, Bernardo Bollen Pinto, Daniel I Bromage, John F Martin, Kevin P Moore, Martin Feelisch, Mervyn Singer
BACKGROUND: Early revascularization of ischemic organs is key to improving outcomes, yet consequent reperfusion injury may be harmful. Reperfusion injury is largely attributed to excess mitochondrial production of reactive oxygen species (ROS). Sulfide inhibits mitochondria and reduces ROS production. Ammonium tetrathiomolybdate (ATTM), a copper chelator, releases sulfide in a controlled and novel manner, and may offer potential therapeutic utility. METHODS AND FINDINGS: In vitro, ATTM releases sulfide in a time-, pH-, temperature-, and thiol-dependent manner...
July 2017: PLoS Medicine
https://www.readbyqxmd.com/read/28677895/overall-survival-in-lower-ipss-risk-mds-by-receipt-of-iron-chelation-therapy-adjusting-for-patient-related-factors-and-measuring-from-time-of-first-red-blood-cell-transfusion-dependence-an-mds-can-analysis
#17
Heather A Leitch, Ambica Parmar, Richard A Wells, Lisa Chodirker, Nancy Zhu, Thomas J Nevill, Karen W L Yee, Brian Leber, Mary-Margaret Keating, Mitchell Sabloff, Eve St Hilaire, Rajat Kumar, Robert Delage, Michelle Geddes, John M Storring, Andrea Kew, April Shamy, Mohamed Elemary, Martha Lenis, Alexandre Mamedov, Jessica Ivo, Janika Francis, Liying Zhang, Rena Buckstein
Analyses suggest iron overload in red blood cell (RBC) transfusion-dependent (TD) patients with myleodysplastic syndrome (MDS) portends inferior overall survival (OS) that is attenuated by iron chelation therapy (ICT) but may be biassed by unbalanced patient-related factors. The Canadian MDS Registry prospectively measures frailty, comorbidity and disability. We analysed OS by receipt of ICT, adjusting for these patient-related factors. TD International Prognostic Scoring System (IPSS) low and intermediate-1 risk MDS, at RBC TD, were included...
July 5, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28677499/protein-phosphatase-1-targeted-small-molecules-iron-chelators-and-curcumin-analogs-as-hiv-1-antivirals
#18
Xionghao Lin, Tatyana Ammosova, Namita Kumari, Sergei Nekhai
Background Despite efficient suppression of HIV-1 replication, current antiviral drugs are not able to eradicate HIV-1 infection. Permanent HIV-1 suppression or complete eradication requires novel biological approaches and therapeutic strategies. Our previous studies showed that HIV-1 transcription is regulated by host cell protein phosphatase-1. We also showed that HIV-1 transcription is sensitive to the reduction of intracellular iron that affects cell cycle-dependent kinase 2. We developed protein phosphatase 1-targeting small molecules that inhibited HIV-1 transcription...
July 4, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28670120/near-infrared-light-triggered-theranostics-for-tumor-specific-enhanced-multimodal-imaging-and-photothermal-therapy
#19
Bo Wu, Bing Wan, Shu-Ting Lu, Kai Deng, Xiao-Qi Li, Bao-Lin Wu, Yu-Shuang Li, Ru-Fang Liao, Shi-Wen Huang, Hai-Bo Xu
The major challenge in current clinic contrast agents (CAs) and chemotherapy is the poor tumor selectivity and response. Based on the self-quench property of IR820 at high concentrations, and different contrast effect ability of Gd-DOTA between inner and outer of liposome, we developed "bomb-like" light-triggered CAs (LTCAs) for enhanced CT/MRI/FI multimodal imaging, which can improve the signal-to-noise ratio of tumor tissue specifically. IR820, Iohexol and Gd-chelates were firstly encapsulated into the thermal-sensitive nanocarrier with a high concentration...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28669771/antidiabetic-antioxidant-and-anti-inflammatory-properties-of-water-and-n-butanol-soluble-extracts-from-saharian-anvillea-radiata-in-high-fat-diet-fed-mice
#20
Chouaib Kandouli, Mathieu Cassien, Anne Mercier, Caroline Delehedde, Emilie Ricquebourg, Pierre Stocker, Mourad Mekaouche, Zineb Leulmi, Aicha Mechakra, Sophie Thétiot-Laurent, Marcel Culcasi, Sylvia Pietri
ETHNOPHARMACOLOGICAL RELEVANCE: According to Saharian traditional medicine, Anvillea radiata Coss. & Dur. (Asteraceae) has been valued for treating a variety of ailments such as gastro-intestinal, liver and pulmonary diseases, and has gained awareness for its beneficial effect on postprandial hyperglycemia. However, to best of our knowledge, no detailed study of the antidiabetic curative effects of this plant has been conducted yet. AIM OF THE STUDY: To determine the hypoglycemic and antidiabetic effect of dietary supplementation with Anvillea radiata extracts on high-fat-diet (HFD)-induced obesity and insulin resistance in C57BL/6J mice in relation with antioxidant, anti-inflammatory, pancreatic beta-cells and skeletal muscle protection, and digestive enzyme inhibiting properties...
July 31, 2017: Journal of Ethnopharmacology
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