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https://www.readbyqxmd.com/read/28100779/intramembrane-proteolysis-of-astrotactins
#1
Hao Chang, Philip M Smallwood, John Williams, Jeremy Nathans
Astrotactins are vertebrate-specific membrane proteins implicated in neuron-glia interactions during central nervous system development and in hair follicle polarity during skin development. By studying epitope-tagged derivatives of mouse Astrotactin2 (Astn2) produced in transfected cells, we determined that the amino- and carboxy-termini reside in the extracellular space and are initially linked by two transmembrane segments and a single cytoplasmic domain. We further show that Astn2 undergoes proteolytic cleavage in the second transmembrane domain (TM2) and that a disulfide bond holds the resulting two fragments together...
January 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28100617/differences-in-glycoprotein-complex-gpc-receptor-binding-site-accessibility-prompt-poor-cross-reactivity-of-neutralizing-antibodies-between-closely-related-arenaviruses
#2
Rachel B Brouillette, Elisabeth K Phillips, Natarajan Ayithan, Wendy Maury
: The glycoprotein complex (GPC) of arenaviruses, composed of stable signal peptide (SSP), GP1, and GP2, is the only antigen correlated with antibody-mediated neutralization. However, despite strong cross-reactivity of convalescent antisera between related arenavirus species, weak or no cross-neutralization occurs. Two closely related Clade B viruses, Machupo virus (MACV) and Junín virus (JUNV), have near identical overall GPC architecture and share a host receptor, transferrin receptor 1...
January 18, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28099381/daily-propranolol-administration-reduces-persistent-injury-associated-anemia-following-severe-trauma-and-chronic-stress
#3
Ines G Alamo, Kolenkode B Kannan, Letitia E Bible, Tyler J Loftus, Harry Ramos, Philip A Efron, Alicia M Mohr
BACKGROUND: Following severe trauma, patients develop a norepinephrine-mediated persistent, injury-associated anemia. This anemia is associated with suppression of bone marrow erythroid colony growth, along with decreased iron levels, and elevated erythropoietin (EPO) levels, which are insufficient to promote effective erythropoiesis. The impact of norepinephrine on iron regulators such as ferroportin, transferrin and transferrin receptor-1 (TFR-1) are unknown. Using a clinically relevant rodent model of lung contusion (LC), hemorrhagic shock (HS), and chronic stress (CS), we hypothesize that daily propranolol (BB), a non-selective beta-blocker, restores bone marrow function and improves iron homeostasis...
January 17, 2017: Journal of Trauma and Acute Care Surgery
https://www.readbyqxmd.com/read/28092401/randomized-clinical-trial-of-preoperative-oral-versus-intravenous-iron-in-anaemic-patients-with-colorectal-cancer
#4
B D Keeler, J A Simpson, O Ng, H Padmanabhan, M J Brookes, A G Acheson
BACKGROUND: Treatment of preoperative anaemia is recommended as part of patient blood management, aiming to minimize perioperative allogeneic red blood cell transfusion. No clear evidence exists outlining which treatment modality should be used in patients with colorectal cancer. The study aimed to compare the efficacy of preoperative intravenous and oral iron in reducing blood transfusion use in anaemic patients undergoing elective colorectal cancer surgery. METHODS: Anaemic patients with non-metastatic colorectal adenocarcinoma were recruited at least 2 weeks before surgery and randomized to receive oral (ferrous sulphate) or intravenous (ferric carboxymaltose) iron...
January 16, 2017: British Journal of Surgery
https://www.readbyqxmd.com/read/28088015/transferrin-gated-mesoporous-silica-nanoparticles-for-redox-responsive-and-targeted-drug-delivery
#5
Xiaolu Chen, Hui Sun, Jun Hu, Xia Han, Honglai Liu, Ying Hu
This work reports on a targeted and controlled drug delivery system based on protein decorated mesoporous silica nanoparticles (MSNs). In this system, transferrin (Tf), a naturally existing protein, is grafted on the surfaces of MSNs via redox-cleavable disulfide bonds, serving as both a capping agent and a targeting ligand simultaneously. The uniform particles with ordered mesoporous structures and the successful construction of the Tf/MSN hybrid nanocarriers can be confirmed through combined techniques. It is found that the model anticancer drug doxorubicin (DOX) can be efficiently encapsulated in the MSNs in the absence of glutathione (GSH), and a burst release of DOX is observed when the system is exposed to GSH, indicating good capping efficiency of Tf and redox-responsive release of DOX...
January 8, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28087910/-progress-on-anti-tumor-molecular-mechanisms-of-dihydroartemisinin
#6
Peng Cao, Dongjin Leng, Ying Li, Ziwei Zhang, Lei Liu, Xiaoyan Li
Artemisinin is an anti-malarial drug with poor water solubility and oral absorption; so a variety of derivatives based on the parent nucleus have been developed. Compared with artemisinin, dihydroartemisinin (DHA) has a stronger anti-malaria activity, and has the advantages of high metabolic rate and better water solubility. Recent studies have discovered that DHA has a good inhibitory effect on tumor cells, which is closely related to the peroxide bridge in its molecular structure. Since tumor cells need more Fe(3+) than normal cells, there are a large number of transferrin receptors on the tumor cell membrane...
May 25, 2016: Zhejiang da Xue Xue Bao. Yi Xue Ban, Journal of Zhejiang University. Medical Sciences
https://www.readbyqxmd.com/read/28087888/simulated-microgravity-decreases-circulating-iron-in-rats-role-of-inflammation-induced-hepcidin-upregulation
#7
Thibault Cavey, Nicolas Pierre, Kévin Nay, Coralie Allain, Martine Ropert, Olivier Loréal, Frédéric Derbré
During spaceflight, humans exposed to microgravity exhibit an increase of iron storage and a reduction of circulating iron. Such perturbations could promote oxidative stress and anemia in astronauts. The mechanism by which microgravity modulates iron metabolism is still unknown. Herein, we hypothesized that microgravity up-regulates hepcidin, a hormone produced by the liver that is the main controller of iron homeostasis. To test this hypothesis, rats were submitted to hindlimb unloading (HU), the reference model to mimic the effects of microgravity in rodents...
January 13, 2017: Experimental Physiology
https://www.readbyqxmd.com/read/28080913/liver-ultrasonography-in-dolphins-use-of-ultrasonography-to-establish-a-technique-for-hepatobiliary-imaging-and-to-evaluate-metabolic-disease-associated-liver-changes-in-bottlenose-dolphins-tursiops-truncatus
#8
Kelsey E Seitz, Cynthia R Smith, Stanley L Marks, Stephanie K Venn-Watson, Marina Ivančić
The objective of this study was to establish a comprehensive technique for ultrasound examination of the dolphin hepatobiliary system and apply this technique to 30 dolphins to determine what, if any, sonographic changes are associated with blood-based indicators of metabolic syndrome (insulin greater than 14 μIU/ml or glucose greater than 112 mg/dl) and iron overload (transferrin saturation greater than 65%). A prospective study of individuals in a cross-sectional population with and without elevated postprandial insulin levels was performed...
December 2016: Journal of Zoo and Wildlife Medicine: Official Publication of the American Association of Zoo Veterinarians
https://www.readbyqxmd.com/read/28075490/soluble-transferrin-receptor-and-risk-of-type-2-diabetes-in-the-obese-and-non-obese
#9
Jose C Fernández-Cao, Victoria Arija, Núria Aranda, Josep Basora, Javier Diez-Espino, Ramón Estruch, Montse Fitó, Dolores Corella D Pharm, Jordi Salas-Salvadó
BACKGROUND: Studies evaluating the relationship between soluble transferrin receptor (sTfR), a biomarker inversely related to body iron stores, and risk of type 2 diabetes mellitus (T2DM) are scarce and inconclusive. Furthermore, sTfR concentrations have been observed to be significantly higher in obese than in non-obese individuals. Therefore, the aim of the present study was to assess the relationship between sTfR and the risk of T2DM in obese and non-obese subjects. DESIGN: A nested case-control study of 153 cases of newly diagnosed diabetic subjects, 73 obese and 80 non-obese, and 306 individually matched-controls, 138 obese and 166 non-obese, who did not develop T2DM for a median 6-year follow-up (interquartile range: 3...
January 11, 2017: European Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28075466/co-delivery-of-doxorubicin-and-ph-sensitive-curcumin-prodrug-by-transferrin-targeted-nanoparticles-for-breast-cancer-treatment
#10
Tongxing Cui, Sihao Zhang, Hong Sun
The natural product curcumin and the chemotherapeutic agent doxorubicin have been used in the treatment of many cancers, including breast cancer. However, fast clearance and unspecific distribution in the body after intravenous injection are still challenges to be overcome by an ideal nano-sized drug delivery system in cancer treatment. In this study we design transferrin (Tf) decorated nanoparticles (NPs) to co-deliver CUR and DOX for breast cancer treatment. A pH-sensitive prodrug, transferrin-poly(ethylene glycol)-curcumin (Tf-PEG-CUR), was synthesized and used for the self‑assembling of NPs (Tf-PEG-CUR NPs)...
February 2017: Oncology Reports
https://www.readbyqxmd.com/read/28075024/uncovering-iron-regulation-with-species-specific-transcriptome-patterns-in-atlantic-and-coho-salmon-during-a-caligus-rogercresseyi-infestation
#11
V Valenzuela-Muñoz, S Boltaña, C Gallardo-Escárate
Salmon species cultured in Chile evidence different levels of susceptibility to the sea louse Caligus rogercresseyi. These differences have mainly been associated with specific immune responses. Moreover, iron regulation seems to be an important mechanism to confer immunity during the host infestation. This response called nutritional immunity has been described in bacterial infections, despite that no comprehensive studies involving in marine ectoparasites infestation have been reported. With this aim, we analysed the transcriptome profiles of Atlantic and coho salmon infected with C...
January 11, 2017: Journal of Fish Diseases
https://www.readbyqxmd.com/read/28069541/a-bispecific-tribody-pet-radioligand-for-visualization-of-amyloid-beta-protofibrils-a-new-concept-for-neuroimaging
#12
Stina Syvänen, Xiaotian T Fang, Greta Hultqvist, Silvio R Meier, Lars Lannfelt, Dag Sehlin
Antibodies are highly specific for their target molecules, but their poor brain penetrance has restricted their use as PET ligands for imaging of targets within the CNS. The aim of this study was to develop an antibody-based radioligand, using the Tribody(TM) format, for PET imaging of soluble amyloid-beta (Aβ) protofibrils, which are suggested to cause neurodegeneration in Alzheimer's disease. Antibodies, even when expressed in smaller engineered formats, are large molecules that do not enter the brain in sufficient amounts for imaging purposes...
January 6, 2017: NeuroImage
https://www.readbyqxmd.com/read/28068331/modelling-systemic-iron-regulation-during-dietary-iron-overload-and-acute-inflammation-role-of-hepcidin-independent-mechanisms
#13
Mihaela Enculescu, Christoph Metzendorf, Richard Sparla, Maximilian Hahnel, Johannes Bode, Martina U Muckenthaler, Stefan Legewie
Systemic iron levels must be maintained in physiological concentrations to prevent diseases associated with iron deficiency or iron overload. A key role in this process plays ferroportin, the only known mammalian transmembrane iron exporter, which releases iron from duodenal enterocytes, hepatocytes, or iron-recycling macrophages into the blood stream. Ferroportin expression is tighly controlled by transcriptional and post-transcriptional mechanisms in response to hypoxia, iron deficiency, heme iron and inflammatory cues by cell-autonomous and systemic mechanisms...
January 9, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28068286/pathobiochemical-mechanisms-relating-iron-homeostasis-to-parameters-of-inflammatory-activity-and-autoimmune-disorders-in-rheumatoid-arthritis
#14
Katya I Stefanova, Ginka T Delcheva, Ana I Maneva, Anastas Z Batalov, Mariela G Geneva-Popova, Rositza V Karalilova, Kiril K Simitchiev
AIM: To find the correlations between the parameters of iron homeostasis, inflammatory activity and autoimmune disorders in rheumatoid arthritis (RA). MATERIALS AND METHODS: The present study included 114 patients with RA and 42 healthy controls. We determined the parameters of iron homeostasis: serum iron, total iron binding capacity (TIBC), ferritin and soluble transferrin receptor (sTfR), the parameters of inflammatory activity: C-reactive protein (CRP), interleukin-6 (IL-6) and prohepcidin, and the parameters of autoimmune disorders: rheumatoid factor (RF), anti-cyclic citrullinated peptide (antiCCP) antibodies, and DAS 28...
December 1, 2016: Folia Medica
https://www.readbyqxmd.com/read/28067430/editorial-process-file-includedexogenous-lysophospholipids-with-large-head-groups-perturb-clathrin-mediated-endocytosis
#15
Ieva Ailte, Anne Berit Dyve Lingelem, Audun Sverre Kvalvaag, Simona Kavaliauskiene, Andreas Brech, Gerbrand Koster, Paul Gunnar Dommersnes, Jonas Bergan, Tore Skotland, Kirsten Sandvig
In this study, we have investigated how clathrin-dependent endocytosis is affected by exogenously added lysophospholipids (LPLs). Addition of LPLs with large head groups strongly inhibits transferrin (Tf) endocytosis in various cell lines, while LPLs with small head groups do not. Electron and total internal reflection fluorescence microscopy (EM and TIRF) reveal that treatment with lysophosphatidylinositol (LPI) with the fatty acyl group C18:0 leads to reduced numbers of invaginated clathrin-coated pits (CCPs) at the plasma membrane, fewer endocytic events per membrane area and increased lifetime of CCPs...
January 9, 2017: Traffic
https://www.readbyqxmd.com/read/28065783/mathematical-modeling-of-mutant-transferrin-crm107-molecular-conjugates-for-cancer-therapy
#16
Dennis J Yoon, Kevin Y Chen, André M Lopes, April A Pan, Joseph Shiloach, Anne B Mason, Daniel T Kamei
The transferrin (Tf) trafficking pathway is a promising mechanism for use in targeted cancer therapy due to the overexpression of transferrin receptors (TfRs) on cancerous cells. We have previously developed a mathematical model of the Tf/TfR trafficking pathway to improve the efficiency of Tf as a drug carrier. By using diphtheria toxin (DT) as a model toxin, we found that mutating the Tf protein to change its iron release rate improves cellular association and efficacy of the drug. Though this is an improvement upon using wild-type Tf as the targeting ligand, conjugated toxins like DT are unfortunately still highly cytotoxic at off-target sites...
January 6, 2017: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/28064007/protein-based-nanotoxicology-assessment-strategy
#17
Marlene Pedersen Elnegaard, Markus List, Helle Christiansen, Steffen Schmidt, Jan Mollenhauer, Ines Block
The nanomaterial community calls for standardized in vitro assays to determine nanoparticle toxicity in the effort to reduce the number of in vivo validation experiments. We demonstrate that chip-based protein detection is suitable for assessing toxicity and may complement traditional assays to improve selection of primary hits for subsequent analysis. As nanodrug mimics, we analyzed the effect of transiently transfected siRNAs in MCF7 breast cancer cells and normal MCF12A breast cells, resembling a differential screen...
January 5, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/28063856/effectiveness-of-deferoxamine-on-ferric-chloride-induced-epilepsy-in-rats
#18
Xiang Zou, Shize Jiang, Zehan Wu, Yimin Shi, Shengyong Cai, Renqing Zhu, Liang Chen
Iron overload has been regarded as a common cause for refractory epilepsies in patients after hemorrhagic strokes. This study is to examine the potential epilepsy control effect of deferoxamine (DFO), an iron chelator, on a ferric chloride-induced epilepsy rat model. Twenty four rats were divided into 4 groups: group I is blank control group, group II is sham group with intracortical injection of saline, group III is epilepsy group with intracortical injection of iron and saline treatment, group IV is treatment group with intracortical injection of iron and DFO treatment...
January 4, 2017: Brain Research
https://www.readbyqxmd.com/read/28057442/iron-importers-zip8-and-zip14-are-expressed-in-retina-and-regulated-by-retinal-iron-levels
#19
Jacob Sterling, Samyuktha Guttha, Ying Song, Delu Song, Majda Hadziahmetovic, Joshua L Dunaief
Intracellular retinal iron accumulation has been implicated in the pathogenesis of age-related macular degeneration (AMD), the leading cause of irreversible blindness among individuals over the age of 50. Ceruloplasmin/hephaestin double knockout mice (Cp/Heph DKO) and hepcidin knockout mice (Hepc KO) accumulate retinal iron and model some features of AMD. Two canonical pathways govern cellular iron import - transferrin-bound iron import and non-transferrin bound iron import. In Cp/Heph DKO and Hepc KO iron-loaded retinas, transferrin-bound iron import is downregulated...
January 2, 2017: Experimental Eye Research
https://www.readbyqxmd.com/read/28056319/-risk-factors-for-lower-extremity-amputation-in-patients-with-diabetic-foot
#20
B Xu, C Z Yang, S B Wu, D Zhang, L N Wang, L Xiao, Y Chen, C R Wang, A Tong, X F Zhou, X H Li, X H Guan
Objective: To explore the risk factors for lower extremity amputation in patients with diabetic foot. Methods: The clinical data of 1 771 patients with diabetic foot at the Air Force General Hospital of PLA from November 2001 to April 2015 were retrospectively analyzed. The patients were divided into the non-amputation and amputation groups. Within the amputation group, subjects were further divided into the minor and major amputation subgroups. Binary logistic regression analyses were used to assess the association between risk factors and lower extremity amputation...
January 1, 2017: Zhonghua Nei Ke za Zhi [Chinese Journal of Internal Medicine]
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