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Modeling Modulation of the Tick Regulome in Response to Anaplasma phagocytophilum for the Identification of New Control Targets
Conclusion Our modeling of the modulation of the tick regulome in response to A. phagocytophilum infection provided new insights into the mechanisms that target specific functions in different tick tissues. These results supported the use of network analysis for the study of regulome response to infection. Although general mechanisms affected by A. phagocytophilum infection may be conserved even between tick and human cells (de la Fuente et al., 2016b), the effect of vector-pathogen co-evolution on pathogen isolates adaptation to grow in tick cells (Alberdi et al., 2015) may result in differences between isolates in the m...
Source: Frontiers in Physiology - April 17, 2019 Category: Physiology Source Type: research

TonEBP Suppresses the HO-1 Gene by Blocking Recruitment of Nrf2 to Its Promoter
Discussion Dynamic changes in the functional phenotype of macrophages are associated with pathogenesis of inflammatory diseases (5–7). TonEBP primes macrophages toward an M1 phenotype, which has pro-inflammatory properties. TonEBP does this by promoting expression of pro-inflammatory genes via interaction with NF-κB (36) and by binding directly to the promoter (37, 64). In addition, TonEBP suppresses expression of the anti-inflammatory cytokine IL-10 by limiting chromatin access to the promoter (37). The pro-inflammatory function of TonEBP suggests that inhibiting its expression or activation could suppres...
Source: Frontiers in Immunology - April 17, 2019 Category: Allergy & Immunology Source Type: research

PGC1 β Regulates Breast Tumor Growth and Metastasis by SREBP1-Mediated HKDC1 Expression
Conclusions: PGC1β regulates breast cancer tumor growth and metastasis by SREBP1-mediated HKDC1 expression. This provides a novel therapeutic strategy through targeting the PGC1β/HKDC1 signaling pathway for breast cancer treatment. Introduction Breast cancer is a very common cancer with significant premature mortality in women. Around 12% of women in USA will have chance to be diagnosed with breast cancer during their lifetimes (1, 2). The development of breast cancer is regulated by many factors, and even as average survival rates have increased significantly as a result of many advanced treatments...
Source: Frontiers in Oncology - April 16, 2019 Category: Cancer & Oncology Source Type: research

Involvement of mitogen-activated protein kinase pathways in ferrous iron-induced aquaporin-4 expression in cultured astrocytes.
In this study, we investigated the effect of ferrous iron overload on AQP4 expression in cultured mouse astrocytes. Primary cultures of astrocytes were exposed to ferrous iron, and the expression of AQP4 as well as the swelling of astrocyte were determined. AQP4 expression was inhibited by small interfering RNA (siRNA). The role of oxidative stress and mitogen-activated protein kinases (MAPKs) signaling pathway in ferrous iron-induced AQP4 expression upregulation were further studied. Ferrous iron exposure induced astrocyte death as well as cell swelling, and increased AQP4 expression. AQP4 gene silencing after siRNA trans...
Source: Neurotoxicology - March 22, 2019 Category: Neurology Authors: Zhong Z, Sun Y, Wang B, Sun Q, Yang G, Bian L Tags: Neurotoxicology Source Type: research

SMAD family member 3 (SMAD3) and SMAD4 repress HIF2{alpha}-dependent iron-regulatory genes Metabolism
Hypoxia-inducible factor 2α (HIF2α) directly regulates a battery of genes essential for intestinal iron absorption. Interestingly, iron deficiency and overload disorders do not result in increased intestinal expression of glycolytic or angiogenic HIF2α target genes. Similarly, inflammatory and tumor foci can induce a distinct subset of HIF2α target genes in vivo. These observations indicate that different stimuli activate distinct subsets of HIF2α target genes via mechanisms that remain unclear. Here, we conducted a high-throughput siRNA-based screen to identify genes that regulate HIF2α's transcriptional activity on...
Source: Journal of Biological Chemistry - March 14, 2019 Category: Chemistry Authors: Xiaoya Ma, Nupur K. Das, Cristina Castillo, Ayla Gourani, Ansu O. Perekatt, Michael P. Verzi, Yatrik M. Shah Tags: Gene Regulation Source Type: research

Magnetically responsive hybrid nanoparticles for in vitro siRNA delivery to breast cancer cells
Publication date: June 2019Source: Materials Science and Engineering: C, Volume 99Author(s): Milene Dalmina, Frederico Pittella, Jelver Alexander Sierra, Gabriela Regina Rosa Souza, Adny Henrique Silva, André Avelino Pasa, Tânia Beatriz Creczynski-PasaAbstractShort interfering RNA (siRNA) showed to be a viable alternative to a better prognosis in cancer therapy. Nevertheless, the successful application of this strategy still depends on the development of nanocarriers for the safe delivery of siRNA into the diseased tissue, which mostly occurs by passive accumulation. When an external magnetic field is applied, magnetic n...
Source: Materials Science and Engineering: C - February 23, 2019 Category: Materials Science Source Type: research

BOLA3 Deficiency Controls Endothelial Metabolism and Glycine Homeostasis in Pulmonary Hypertension.
CONCLUSIONS: BOLA3 acts as a crucial lynchpin connecting Fe-S-dependent oxidative respiration and glycine homeostasis with endothelial metabolic re-programming critical to PH pathogenesis. These results provide a molecular explanation for the clinical associations linking PH with hyperglycinemic syndromes and mitochondrial disorders. These findings also identify novel metabolic targets, including those involved in epigenetics, iron-sulfur biogenesis, and glycine biology, for diagnostic and therapeutic development. PMID: 30759996 [PubMed - as supplied by publisher]
Source: Circulation - February 14, 2019 Category: Cardiology Authors: Yu Q, Tai YY, Tang Y, Zhao J, Negi V, Culley MK, Pilli J, Sun W, Brugger K, Mayr J, Saggar R, Saggar R, Wallace WD, Ross DJ, Waxman AB, Wendell SG, Mullett SJ, Sembrat J, Rojas M, Khan OF, Dahlman JE, Sugahara M, Kagiyama N, Satoh T, Zhang M, Feng N, Gorc Tags: Circulation Source Type: research

Biodistribution and Toxicity Assessment of Superparamagnetic Iron Oxide Nanoparticles In Vitro and In Vivo
This study aimed to examine the toxicity and biodistribution of SPION coated with polyethylenimine (PEI) (SPION-PEI) designed for small interfering RNA (siRNA) delivery bothin vitro andin vivo. SPION-PEI/siRNA complexes were prepared at different weight ratios. Cytotoxic effects of SPION-PEI/siRNA on HSC-T6 cell viability were determined by using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT). Rats were divided into three groups: a control group, a normal-saline group and a SPION-PEI/siRNA group. After a single intravenous injection,in vivo nanoparticle biodistribution and accumulation were evaluated ...
Source: Journal of Huazhong University of Science and Technology -- Medical Sciences -- - December 1, 2018 Category: Research Source Type: research

Novel Insights Into Systemic Iron Regulation
Iron, an essential element in mammals, is absorbed by duodenal enterocytes, enters the circulation through the iron exporter ferroportin, (FPN), circulates bound to transferrin and is uptaken through Transferrin Receptor 1. If in excess, iron is stored in macrophages and hepatocytes and released when needed. To maintain systemic iron homeostasis and to avoid the formation of "non transferrin bound iron" (NTBI), a highly reactive form which causes organ damage, the liver synthetizes hepcidin that, binding FPN, blocks iron export to the circulation. Hepcidin integrates signals from body iron, erythropoiesis and inflammatory ...
Source: Blood - November 21, 2018 Category: Hematology Authors: Silvestri, L., Pagani, A., Nai, A., Camaschella, C. Tags: Swinging the Iron Pendulum: Loss and Gain Through Blood Donation and Transfusion Source Type: research

NCOA4 Mediates Mobilization of Hepatic Iron Stores after Blood Loss
The intracellular protein NCOA4 mediates the autophagic degradation of ferritin in vitro (Mancias et al., Nature 2014; Dowdle et al., Nat Cell Biol 2014); mice with global Ncoa4 disruption show hyperferremia, microcytic anemia, and ferritin accumulation in multiple organs, including liver (Bellelli et al., Cell Rep 2016). Here, we dissect the requirement for NCOA4 in hepatic iron mobilization after acute blood loss, using Ncoa4-targeting siRNA that was conjugated to triantennary N-acetylgalactosamine (GalNAc-Ncoa4 siRNA) to promote uptake by hepatocytes. On experimental day 0, 8-week-old female C57BL/6N mice underwent a si...
Source: Blood - November 21, 2018 Category: Hematology Authors: Li, X., Lozovatsky, L., Liu, D., Ayala-Lopez, N., Finberg, K. E. Tags: 102. Regulation of Iron Metabolism: Poster I Source Type: research

The Abnormal Expression and Mutation of Recombination Signal Binding Protein-Jk Gene Mightbe Contribute to the Proliferation of CD59- Clone in Paroxysmal Nocturnal Hemoglobinuria Patients
Conclusion: High expressed RBPJ was associated with hemolysis index in PNH, and inhibiting it can induced the apoptosis of PNH primary cells in vitro, indicating RBPJ may be involved in the proliferation of PNH clones.Figure.DisclosuresNo relevant conflicts of interest to declare.
Source: Blood - November 21, 2018 Category: Hematology Authors: Fu, R., LI, L., Liu, Z., Liu, H., Wang, H., Chen, Y., Shao, Z. Tags: 101. Red Cells and Erythropoiesis, Structure and Function, Metabolism, and Survival, Excluding Iron: Poster III Source Type: research

SLN124, a Galnac-siRNA Conjugate Targeting TMPRSS6, for the Treatment of Iron Overload and Ineffective Erythropoiesis Such As in Beta-Thalassemia
Accumulation of excess iron in tissues causes organ damage and dysfunction and may lead to serious clinical consequences including liver cirrhosis, diabetes, growth retardation and heart failure. Iron overload is a major health threat in iron loading anemias, like beta-thalassemia, myelodysplastic syndrome and in hereditary hemochromatosis. In patients with beta-thalassemia major, iron overload develops due to frequent blood transfusions to control the severe anemia. In addition, iron overload also occurs in patients with beta thalassemia intermedia (non-transfusion dependent beta-thalassemia). In the later cases, iron ove...
Source: Blood - November 21, 2018 Category: Hematology Authors: Altamura, S., Altamura, S., Muckenthaler, M. U., Dames, S., Frauendorf, C., Schubert, S., Aleku, M., Vadolas, J., Grigoriadis, G., Zugel, U. Tags: 102. Regulation of Iron Metabolism: Poster II Source Type: research

The roles of hypoxia-inducible Factor-1 and iron regulatory protein 1 in iron uptake induced by acute hypoxia.
CONCLUSIONS: We propose that HIF-1/HRE system might play a principal part in hypoxia induced iron uptake. PMID: 30415773 [PubMed - as supplied by publisher]
Source: Biochemical and Biophysical Research communications - November 8, 2018 Category: Biochemistry Authors: Yang L, Wang D, Wang XT, Lu YP, Zhu L Tags: Biochem Biophys Res Commun Source Type: research

Worm ‐Like Biomimetic Nanoerythrocyte Carrying siRNA for Melanoma Gene Therapy
This study reports a third type of nanoworm, biomimetic nanoerythrocytes for siRNA delivery, except for filomicelle and nanoworm iron ‐oxide particle, which is the first approach that allows for targeted siRNA delivery by a process involving red blood cell (RBC) membrane cloaking of charge‐reversible polyplexes of siRNA and polycation. RBC membrane cloaking protects siRNA from RNase A degradation. Moreover, the RBC membrane‐ cloaked charge‐reversible siRNA vector (RBC‐reversible polyplex (RP)) not only stays longer in the blood circulation than that of negatively charged bovine serum albumin (BSA) spheres and pos...
Source: Small - October 17, 2018 Category: Nanotechnology Authors: Yanming Wang, Xin Ji, Miaoliang Ruan, Wen Liu, Rongguang Song, Jian Dai, Wei Xue Tags: Full Paper Source Type: research

High-content analysis for mitophagy response to nanoparticles: A potential sensitive biomarker for nanosafety assessment
Publication date: Available online 20 September 2018Source: Nanomedicine: Nanotechnology, Biology and MedicineAuthor(s): Chengyong He, Shengwei Jiang, Huan Yao, Liyin Zhang, Chuanli Yang, Shan Jiang, Fengkai Ruan, Denglin Zhan, Gang Liu, Zhongning Lin, Yuchun Lin, Xiaoyuan ChenAbstractMitophagy, a selective autophagy of mitochondria, clears up damaged mitochondria to maintain cell homeostasis. We performed high-content analysis (HCA) to detect the increase of PINK1, an essential protein controlling mitophagy, in hepatic cells treated with several nanoparticles (NPs). PINK1 immunofluorescence-based HCA was more sensitive th...
Source: Nanomedicine: Nanotechnology, Biology and Medicine - September 21, 2018 Category: Nanotechnology Source Type: research