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https://www.readbyqxmd.com/read/28817646/genetic-dissection-of-endothelial-transcriptional-activity-of-zebrafish-aryl-hydrocarbon-receptors-ahrs
#1
Wade W Sugden, Roberto C Leonardo-Mendonça, Darío Acuña-Castroviejo, Arndt F Siekmann
The aryl hydrocarbon receptor (AHR) is a basic helix-loop-helix transcription factor conserved across phyla from flies to humans. Activated by a number of endogenous ligands and environmental toxins, studies on AHR function and gene regulation have largely focused on a toxicological perspective relating to aromatic hydrocarbons generated by human activities and the often-deleterious effects of exposure on vertebrates mediated by AHR activation. A growing body of work has highlighted the importance of AHR in physiologic processes, including immune cell differentiation and vascular patterning...
2017: PloS One
https://www.readbyqxmd.com/read/28816367/the-in-vitro-and-in-vivo-antiangiogenic-effects-of-flavokawain-b
#2
Mariana C Rossette, Débora C Moraes, Erika K Sacramento, Marco Aurélio Romano-Silva, Juliana L Carvalho, Dawidson A Gomes, Hanna Caldas, Eitan Friedman, Luciana Bastos-Rodrigues, Luiz De Marco
Angiogenesis is implicated in the development of a variety of pathological processes, most commonly cancer. It is essential for tumor growth and metastasis, making it an important cancer therapeutic target. Naturally occurring substances have led to the discovery of anticancer agents. Flavokawain B (FKB), a chalcone isolated from the root extracts of kava-kava plant, inhibits proliferation and causes apoptosis in vitro and in vivo of various cancer cell lines. The antimetastatic potential of FKB has also been suggested...
August 17, 2017: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/28811218/wnt-signaling-positively-regulates-endothelial-cell-fate-specification-in-the-fli1a-positive-progenitor-population-via-lef1
#3
Kathleen Hübner, Kathrin S Grassme, Jyoti Rao, Nina K Wenke, Cordula L Zimmer, Laura Korte, Katja Mu Ller, Saulius Sumanas, Boris Greber, Wiebke Herzog
During vertebrate embryogenesis, vascular endothelial cells (ECs) and primitive erythrocytes become specified within close proximity in the posterior lateral plate mesoderm (LPM) from a common progenitor. However, the signaling cascades regulating the specification into either lineage remain largely elusive. Here, we analyze the contribution of β-catenin dependent Wnt signaling to EC and erythrocyte specification during zebrafish embryogenesis. We generated novel β-catenin dependent Wnt signaling reporters which, by using destabilized fluorophores (Venus-Pest, dGFP), specifically allow us to detect Wnt signaling responses in narrow time windows as well as in spatially restricted domains, defined by Cre recombinase expression (Tg(axin2BAC:Venus-Pest)(mu288); Tg(14TCF:loxP-STOP-loxP-dGFP)(mu202))...
August 12, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28803829/the-vascular-niche-regulates-hematopoietic-stem-and-progenitor-cell-lodgment-and-expansion-via-klf6a-ccl25b
#4
Yuanyuan Xue, Junhua Lv, Chunxia Zhang, Lu Wang, Dongyuan Ma, Feng Liu
In mammals, hematopoietic stem and progenitor cells (HSPCs) rapidly expand in the fetal liver (FL), but the underlying mechanism remains unclear. Here, we characterize zebrafish caudal hematopoietic tissue (CHT) and identify an important cellular and molecular mechanism of HSPC expansion. Time-lapse imaging showed that HSPCs localize adjacent to vascular endothelial cells (ECs), and their migration and expansion display caudal vein-specific orientation in the CHT. RNA sequencing and functional analysis identified that an EC-expressed transcription factor, Krüppel-like factor 6a (Klf6a), is essential for the CHT niche...
August 9, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28790366/amotl2-integrates-polarity-and-junctional-cues-to-modulate-cell-shape
#5
Sara Hultin, Aravindh Subramani, Sebastian Hildebrand, Yujuan Zheng, Arindam Majumdar, Lars Holmgren
The assembly of individual epithelial or endothelial cells into a tight cellular sheet requires stringent control of cell packing and organization. These processes are dependent on the establishment and further integration of cellular junctions, the cytoskeleton and the formation of apical-basal polarity. However, little is known how these subcellular events are coordinated. The (Angiomotin) Amot protein family consists of scaffold proteins that interact with junctional cadherins, polarity proteins and the cytoskeleton...
August 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28762754/flow-responsive-vegfr-pkc%C3%A9-signaling-mediates-glycolytic-metabolites-for-vascular-repair
#6
Kyung In Baek, Rongsong Li, Nelson Jen, Howard Choi, Amir Kaboodrangi, Peipei Ping, David Liem, Tyler Beebe, Tzung K Hsiai
Aims - Hemodynamic shear stress participates in maintaining vascular redox status. Elucidating flow-mediated endothelial metabolites enables us to discover metabolic biomarkers and therapeutic targets. We posited that flow-responsive VEGF receptor-PKCɛ-PFKFB3 signaling modulates glycolytic metabolites for vascular repair. Results - Bidirectional oscillatory flow (OSS: 0.1 ± 3 dyne·cm<sup>-2</sup> at 1 Hz) up-regulated VEGFR-dependent PKCɛ expression to a greater degree than did unidirectional pulsatile flow (PSS: 23 ± 8 dyne·cm<sup>-2</sup> at 1 Hz) in human aortic endothelial cells (HAEC) (<i>p < 0...
August 1, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28744122/penetration-of-blood-brain-barrier-and-antitumor-activity-and-nerve-repair-in-glioma-by-doxorubicin-loaded-monosialoganglioside-micelles-system
#7
Dan Zou, Wei Wang, Daoxi Lei, Ying Yin, Peng Ren, Jinju Chen, Tieying Yin, Bochu Wang, Guixue Wang, Yazhou Wang
For the treatment of glioma and other central nervous system diseases, one of the biggest challenges is that most therapeutic drugs cannot be delivered to the brain tumor tissue due to the blood-brain barrier (BBB). The goal of this study was to construct a nanodelivery vehicle system with capabilities to overcome the BBB for central nervous system administration. Doxorubicin as a model drug encapsulated in ganglioside GM1 micelles was able to achieve up to 9.33% loading efficiency and 97.05% encapsulation efficiency by orthogonal experimental design...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28723572/robust-identification-of-developmentally-active-endothelial-enhancers-in-zebrafish-using-fans-assisted-atac-seq
#8
Aurelie Quillien, Mary Abdalla, Jun Yu, Jianhong Ou, Lihua Julie Zhu, Nathan D Lawson
Identification of tissue-specific and developmentally active enhancers provides insights into mechanisms that control gene expression during embryogenesis. However, robust detection of these regulatory elements remains challenging, especially in vertebrate genomes. Here, we apply fluorescent-activated nuclei sorting (FANS) followed by Assay for Transposase-Accessible Chromatin with high-throughput sequencing (ATAC-seq) to identify developmentally active endothelial enhancers in the zebrafish genome. ATAC-seq of nuclei from Tg(fli1a:egfp)(y1) transgenic embryos revealed expected patterns of nucleosomal positioning at transcriptional start sites throughout the genome and association with active histone modifications...
July 18, 2017: Cell Reports
https://www.readbyqxmd.com/read/28714969/endothelial-notch-signalling-limits-angiogenesis-via-control-of-artery-formation
#9
Sana S Hasan, Roman Tsaryk, Martin Lange, Laura Wisniewski, John C Moore, Nathan D Lawson, Karolina Wojciechowska, Hans Schnittler, Arndt F Siekmann
Angiogenic sprouting needs to be tightly controlled. It has been suggested that the Notch ligand dll4 expressed in leading tip cells restricts angiogenesis by activating Notch signalling in trailing stalk cells. Here, we show using live imaging in zebrafish that activation of Notch signalling is rather required in tip cells. Notch activation initially triggers expression of the chemokine receptor cxcr4a. This allows for proper tip cell migration and connection to the pre-existing arterial circulation, ultimately establishing functional arterial-venous blood flow patterns...
August 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28697965/beyond-organoids-in-vitro-vasculogenesis-and-angiogenesis-using-cells-from-mammals-and-zebrafish
#10
REVIEW
Muhammad Ibrahim, Michael K Richardson
The ability to culture complex organs is currently an important goal in biomedical research. It is possible to grow organoids (3D organ-like structures) in vitro; however, a major limitation of organoids, and other 3D culture systems, is the lack of a vascular network. Protocols developed for establishing in vitro vascular networks typically use human or rodent cells. A major technical challenge is the culture of functional (perfused) networks. In this rapidly advancing field, some microfluidic devices are now getting close to the goal of an artificially perfused vascular network...
July 8, 2017: Reproductive Toxicology
https://www.readbyqxmd.com/read/28684310/selective-inhibition-of-plasma-membrane-calcium-atpase-4-improves-angiogenesis-and-vascular-reperfusion
#11
Sathishkumar Kurusamy, Dolores López-Maderuelo, Robert Little, David Cadagan, Aaron M Savage, Jude C Ihugba, Rhiannon R Baggott, Farjana B Rowther, Sara Martínez-Martínez, Pablo Gómez-Del Arco, Clare Murcott, Weiguang Wang, J Francisco Nistal, Delvac Oceandy, Ludwig Neyses, Robert N Wilkinson, Elizabeth J Cartwright, Juan Miguel Redondo, Angel Luis Armesilla
AIMS: Ischaemic cardiovascular disease is a major cause of morbidity and mortality worldwide. Despite promising results from pre-clinical animal models, VEGF-based strategies for therapeutic angiogenesis have yet to achieve successful reperfusion of ischaemic tissues in patients. Failure to restore efficient VEGF activity in the ischaemic organ remains a major problem in current pro-angiogenic therapeutic approaches. Plasma membrane calcium ATPase 4 (PMCA4) negatively regulates VEGF-activated angiogenesis via inhibition of the calcineurin/NFAT signalling pathway...
July 3, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28675847/mononuclear-gold-iii-complexes-with-phenanthroline-ligands-as-efficient-inhibitors-of-angiogenesis-a-comparative-study-with-auranofin-and-sunitinib
#12
Aleksandar Pavic, Biljana Đ Glišić, Sandra Vojnovic, Beata Warżajtis, Nada D Savić, Marija Antić, Slavko Radenković, Goran V Janjić, Jasmina Nikodinovic-Runic, Urszula Rychlewska, Miloš I Djuran
Gold(III) complexes with 1,7- and 4,7-phenanthroline ligands, [AuCl3(1,7-phen-κN7)] (1) and [AuCl3(4,7-phen-κN4)] (2) were synthesized and structurally characterized by spectroscopic (NMR, IR and UV-vis) and single-crystal X-ray diffraction techniques. In these complexes, 1,7- and 4,7-phenanthrolines are monodentatedly coordinated to the Au(III) ion through the N7 and N4 nitrogen atoms, respectively. In comparison to the clinically relevant anti-angiogenic compounds auranofin and sunitinib, gold(III)-phenanthroline complexes showed from 1...
September 2017: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/28653157/computational-analysis-on-down-regulated-images-of-macrophage-scavenger-receptor
#13
Byeongtaek Oh, Yugyung Lee, Mingui Fu, Chi H Lee
BACKGROUND: Thiolated-graphene quantum dots (SH-GQDs) were developed and assessed for an efficient preventive means against atherosclerosis and potential toxicity through computational image analysis and animal model studies. EXPERIMENTS: Zebrafish (wild-type, wt) were used for evaluation of toxicity through the assessment of embryonic mortality, malformation and ROS generation. The amounts of SH-GQDs uptaken by mouse macrophage cells (Raw264.7) were analyzed using a flow cytometer...
June 26, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28642593/transforming-growth-factor-%C3%AE-1-regulates-the-nascent-hematopoietic-stem-cell-niche-by-promoting-gluconeogenesis
#14
C-Y Zhang, H-M Yin, H Wang, D Su, Y Xia, L-F Yan, B Fang, W Liu, Y-M Wang, A-H Gu, Y Zhou
The understanding of hematopoietic stem cell (HSC) emergence is important to generate HSCs from pluripotent precursors. However, integrated signaling network that regulates the niche of nascent HSCs remains unclear. Herein, we uncovered a novel role of TGF-β1 in the metabolic niche of HSC emergence using the tgf-β1b(-/-) zebrafish. Our findings first showed that Tgf-β1 transcripts were enriched in the nascent HSCs. Loss of tgf-β1b caused a decrease of nascent HSCs within the aorta-gonad-mesonephros. Moreover, tgf-β1b(+) cells were runx1(+) HSCs and underwent an endothelial-to-hematopoietic-transition process...
June 23, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28621424/ocular-vessel-patterning-in-zebrafish-is-indirectly-regulated-by-hedgehog-signaling
#15
Omri Weiss, Rivka Kaufman, Eyal Mishani, Adi Inbal
The superficial ocular vasculature of the embryonic zebrafish develops in a highly stereotypic manner and hence provides a convenient model for studying molecular mechanisms that regulate vascular patterning. We have used transgenic zebrafish embryos in which all endothelial cells express enhanced Green Fluorescent Protein and small molecule inhibitors to examine the contribution of two signaling pathways, vascular endothelial growth factor (VEGF) and Hedgehog (Hh) pathways, to the development of the superficial system...
2017: International Journal of Developmental Biology
https://www.readbyqxmd.com/read/28619820/soxf-factors-induce-notch1-expression-via-direct-transcriptional-regulation-during-early-arterial-development
#16
Ivy Kim-Ni Chiang, Martin Fritzsche, Cathy Pichol-Thievend, Alice Neal, Kelly Holmes, Anne Lagendijk, Jeroen Overman, Donatella D'Angelo, Alice Omini, Dorien Hermkens, Emmanuelle Lesieur, Ke Liu, Indrika Ratnayaka, Monica Corada, George Bou-Gharios, Jason Carroll, Elisabetta Dejana, Stefan Schulte-Merker, Benjamin Hogan, Monica Beltrame, Sarah De Val, Mathias Francois
Arterial specification and differentiation are influenced by a number of regulatory pathways. While it is known that the Vegfa-Notch cascade plays a central role, the transcriptional hierarchy controlling arterial specification has not been fully delineated. To elucidate the direct transcriptional regulators of Notch receptor expression in arterial endothelial cells, we used histone signatures, DNaseI hypersensitivity and ChIP-seq data to identify enhancers for the human NOTCH1 and zebrafish notch1b genes. These enhancers were able to direct arterial endothelial cell-restricted expression in transgenic models...
July 15, 2017: Development
https://www.readbyqxmd.com/read/28617813/identification-of-padi2-as-a-novel-angiogenesis-regulating-gene-by-genome-association-studies-in-mice
#17
Mehrdad Khajavi, Yi Zhou, Amy E Birsner, Lauren Bazinet, Amanda Rosa Di Sant, Alex J Schiffer, Michael S Rogers, Subrahmanian Tarakkad Krishnaji, Bella Hu, Vy Nguyen, Leonard Zon, Robert J D'Amato
Recent findings indicate that growth factor-driven angiogenesis is markedly influenced by genetic variation. This variation in angiogenic responsiveness may alter the susceptibility to a number of angiogenesis-dependent diseases. Here, we utilized the genetic diversity available in common inbred mouse strains to identify the loci and candidate genes responsible for differences in angiogenic response. The corneal micropocket neovascularization assay was performed on 42 different inbred mouse strains using basic fibroblast growth factor (bFGF) pellets...
June 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28589128/low-density-lipoprotein-receptor-related-protein-1-signaling-in-angiogenesis
#18
REVIEW
Hua Mao, Liang Xie, Xinchun Pi
Low-density lipoprotein receptor-related protein-1 (LRP1) plays multifunctional roles in lipid homeostasis, signaling transduction, and endocytosis. It has been recognized as an endocytic receptor for many ligands and is involved in the signaling pathways of many growth factors or cytokines. Dysregulation of LRP1-dependent signaling events contributes to the development of pathophysiologic processes such as Alzheimer's disease, atherosclerosis, inflammation, and coagulation. Interestingly, recent studies have linked LRP1 with endothelial function and angiogenesis, which has been underappreciated for a long time...
2017: Frontiers in Cardiovascular Medicine
https://www.readbyqxmd.com/read/28578380/the-zebrafish-ventricle-a-hub-of-cardiac-endothelial-cells-for-in-vitro-cell-behavior-studies
#19
Chinmoy Patra, Zacharias Kontarakis, Harmandeep Kaur, Amey Rayrikar, Debanjan Mukherjee, Didier Y R Stainier
Despite our increasing understanding of zebrafish heart development and regeneration, there is limited information about the distribution of endothelial cells (ECs) in the adult zebrafish heart. Here, we investigate and compare the distribution of cardiac ECs (cECs) in adult mouse and zebrafish ventricles. Surprisingly, we find that (i) active coronary vessel growth is present in adult zebrafish, (ii) ~37 and ~39% of cells in the zebrafish heart are ECs and cardiomyocytes, respectively, a composition similar to that seen in mouse...
June 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28574600/diallyl-trisulfides-a-natural-histone-deacetylase-inhibitor-attenuate-hif-1%C3%AE-synthesis-and-decreases-breast-cancer-metastasis
#20
Zhonghong Wei, Yunlong Shan, Li Tao, Yuping Liu, Zhijie Zhu, Zhaoguo Liu, Yuanyuan Wu, Wenxing Chen, Aiyun Wang, Yin Lu
Intratumoral hypoxia promotes the distant metastasis of cancer subclones. The clinical expression level of hypoxia-inducible factor-1α (HIF-1α) reflects the prognosis of a variety of cancers, especially breast cancer. Histone deacetylase (HDAC) inhibitors can target HIF-1α protein due to von Hippel-Lindau protein-dependent degradation. Dietary organosulfur compounds, such as those in garlic, have been reported as HDAC inhibitors. The effects of diallyl sulfide (DAS), diallyl disulfide (DADS) and diallyl trisulfide (DATS) on the ratio of firefly/Renilla luciferase activity in hypoxic MDA-MB-231 cells were determined...
June 2, 2017: Molecular Carcinogenesis
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