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https://www.readbyqxmd.com/read/28938553/homocysteine-induced-peripheral-microcirculation-dysfunction-in-zebrafish-and-its-attenuation-by-l-arginine
#1
Sang Joon Lee, Sung Ho Park, Jinhyuk Fred Chung, Woorak Choi, Hyung Kyu Huh
Elevated blood homocysteine (Hcy) level is frequently observed in aged individuals and those with age-related vascular diseases. However, its effect on peripheral microcirculation is still not fully understood. Using in vivo zebrafish model, the degree of Hcy-induced peripheral microcirculation dysfunction is assessed in this study with a proposed dimensionless velocity parameter [Formula: see text], where [Formula: see text] and [Formula: see text] represent the peripheral microcirculation perfusion and the systemic perfusion levels, respectively...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938538/mir-23a-targets-runx2-and-suppresses-ginsenoside-rg1-induced-angiogenesis-in-endothelial-cells
#2
Xiao-Dong Wu, Ting Guo, Li Liu, Chao Wang, Kun Zhang, Han-Qiang Liu, Feng Wang, Wen-Dong Bai, Meng-Yao Zhang
Rg1 is a predominant protopanaxatriol-type of ginsenoside found in Panax ginseng, and it has been shown to have anti-cancer effects in multiple types of cancer cells. However, Rg1 also induces the expression of proangiogenic factors, such as vascular endothelial growth factor (VEGF-A), in endothelial cells. Unfortunately, angiogenesis positively correlates with cancer development. In this study, we identified RUNX2 as a regulator of ginsenoside Rg1-induced angiogenesis for the first time. We found that RUNX2 was directly targeted and regulated by miR-23a...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28936181/novel-heparin-receptor-transmembrane-protein-184a-regulates-angiogenesis-in-the-adult-zebrafish-caudal-fin
#3
Sara Lynn N Farwell, Kimberly G Reylander, M Kathryn Iovine, Linda J Lowe-Krentz
Transmembrane protein 184A (TMEM184A) was recently identified as the heparin receptor in vascular cells. Heparin binds specifically to TMEM184A and induces anti-proliferative signaling in vitro. Though it is highly conserved, the physiological function of TMEM184A remains unknown. The objective of this study was to investigate the expression and effects on vascular regeneration of TMEM184A using the adult zebrafish regenerating caudal fin as an in vivo model. Here, we show that Tmem184a is expressed in vascular endothelial cells (ECs) of mature and regenerating zebrafish fins...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28934690/butyl-benzyl-phthalate-bbp-induces-caudal-defects-during-embryonic-development
#4
Nicole M Roy, Ewelina Zambrzycka, Jenna Santangelo
Butyl benzyl phthalate (BBP) is commonly added during the manufacturing of plastics to increase flexibility and elasticity. However, BBP leaches off of plastic and environment presence has been detected in soil, groundwater and sediment potentially effecting organisms in the environment. Given the widespread uses of BBP in household, consumer goods and the presence of BBP in the environment, studies on developmental toxicity are needed. Here, we use a zebrafish model to investigate the early developmental toxicity of BBP...
September 18, 2017: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/28925392/atypical-e2fs-inhibit-tumor-angiogenesis
#5
B G M W Weijts, B Westendorp, B T Hien, L M Martínez-López, M Zijp, I Thurlings, R E Thomas, S Schulte-Merker, W J Bakker, A de Bruin
Atypical E2F transcription factors (E2F7 and E2F8) function as key regulators of cell cycle progression and their inactivation leads to spontaneous cancer formation in mice. However, the mechanism of the tumor suppressor functions of E2F7/8 remain obscure. In this study we discovered that atypical E2Fs control tumor angiogenesis, one of the hallmarks of cancer. We genetically inactivated atypical E2Fs in epithelial and mesenchymal neoplasm and analyzed blood vessel formation in three different animal models of cancer...
September 18, 2017: Oncogene
https://www.readbyqxmd.com/read/28855341/cns-resident-progenitors-direct-the-vascularization-of-neighboring-tissues
#6
Ryota L Matsuoka, Andrea Rossi, Oliver A Stone, Didier Y R Stainier
Organ growth requires the coordinated invasion and expansion of blood vessel networks directed by tissue-resident cells and morphogenetic cues. A striking example of this intercellular communication is the vascularization of the central nervous system (CNS), which is driven by neuronal progenitors, including neuroepithelial cells and radial glia. Although the importance of neuronal progenitors in vascular development within the CNS is well recognized, how these progenitors regulate the vasculature outside the CNS remains largely unknown...
August 30, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28854362/loss-of-apela-peptide-in-mice-causes-low-penetrance-embryonic-lethality-and-defects-in-early-mesodermal-derivatives
#7
Laina Freyer, Chih-Wei Hsu, Sonja Nowotschin, Andrea Pauli, Junji Ishida, Keiji Kuba, Akiyoshi Fukamizu, Alexander F Schier, Pamela A Hoodless, Mary E Dickinson, Anna-Katerina Hadjantonakis
Apela (also known as Elabela, Ende, and Toddler) is a small signaling peptide that activates the G-protein-coupled receptor Aplnr to stimulate cell migration during zebrafish gastrulation. Here, using CRISPR/Cas9 to generate a null, reporter-expressing allele, we study the role of Apela in the developing mouse embryo. We found that loss of Apela results in low-penetrance cardiovascular defects that manifest after the onset of circulation. Three-dimensional micro-computed tomography revealed a higher penetrance of vascular remodeling defects, from which some mutants recover, and identified extraembryonic anomalies as the earliest morphological distinction in Apela mutant embryos...
August 29, 2017: Cell Reports
https://www.readbyqxmd.com/read/28851992/tcf7l2-plays-pleiotropic-roles-in-the-control-of-glucose-homeostasis-pancreas-morphology-vascularization-and-regeneration
#8
Nicola Facchinello, Estefania Tarifeño-Saldivia, Enrico Grisan, Marco Schiavone, Margherita Peron, Alessandro Mongera, Olivier Ek, Nicole Schmitner, Dirk Meyer, Bernard Peers, Natascia Tiso, Francesco Argenton
Type 2 diabetes (T2D) is a disease characterized by impaired insulin secretion. The Wnt signaling transcription factor Tcf7l2 is to date the T2D-associated gene with the largest effect on disease susceptibility. However, the mechanisms by which TCF7L2 variants affect insulin release from β-cells are not yet fully understood. By taking advantage of a tcf7l2 zebrafish mutant line, we first show that these animals are characterized by hyperglycemia and impaired islet development. Moreover, we demonstrate that the zebrafish tcf7l2 gene is highly expressed in the exocrine pancreas, suggesting potential bystander effects on β-cell growth, differentiation and regeneration...
August 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28851572/zebrafish-as-an-early-stage-screening-tool-to-study-the-systemic-circulation-of-nanoparticulate-drug-delivery-systems-in-vivo
#9
Sandro Sieber, Philip Grossen, Pascal Detampel, Salome Siegfried, Dominik Witzigmann, Jörg Huwyler
Nanomedicines have gained much attention for the delivery of small molecules or nucleic acids as treatment options for many diseases. However, the transfer from experimental systems to in vivo applications remains a challenge since it is difficult to assess their circulation behavior in the body at an early stage of drug discovery. Thus, innovative and improved concepts are urgently needed to overcome this issue and to close the gap between empiric nanoparticle design, in vitro assessment, and first in vivo experiments using rodent animal models...
August 26, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28845297/discovery-of-a-rock-inhibitor-fpnd-which-prevents-cerebral-hemorrhage-through-maintaining-vascular-integrity-by-interference-with-ve-cadherin
#10
Shang Li, Nana Ai, Mingyun Shen, Yuanye Dang, Cheong-Meng Chong, Peichen Pan, Yiu Wa Kwan, Shun Wan Chan, George Pak Heng Leung, Maggie Pui Man Hoi, Tingjun Hou, Simon Ming-Yuen Lee
Hemorrhagic stroke occurs when a weakened vessel ruptures and bleeds into the surrounding brain, leading to high rates of death and disability worldwide. A series of complex pathophysiological cascades contribute to the risk of hemorrhagic stroke, and no therapies have proven effective to prevent hemorrhagic stroke. Stabilization of vascular integrity has been considered as a potential therapeutic target for hemorrhagic stroke. ROCKs, which belong to the serine/threonine protein kinase family and participate in the organization of actin cytoskeleton, have become attractive targets for the treatment of strokes...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28836097/animal-models-of-diabetic-retinopathy
#11
REVIEW
Ana Maria Olivares, Kristen Althoff, Gloria Fanghua Chen, Siqi Wu, Margaux A Morrisson, Margaret M DeAngelis, Neena Haider
PURPOSE OF REVIEW: Diabetic retinopathy (DR) is one of the most common complications associated with chronic hyperglycemia seen in patients with diabetes mellitus. While many facets of DR are still not fully understood, animal studies have contributed significantly to understanding the etiology and progression of human DR. This review provides a comprehensive discussion of the induced and genetic DR models in different species and the advantages and disadvantages of each model. RECENT FINDINGS: Rodents are the most commonly used models, though dogs develop the most similar morphological retinal lesions as those seen in humans, and pigs and zebrafish have similar vasculature and retinal structures to humans...
August 24, 2017: Current Diabetes Reports
https://www.readbyqxmd.com/read/28817784/hydrogen-peroxide-regulates-angiogenesis-related-factors-in-tumor-cells
#12
Ana Jerónimo, Gonçalo Rodrigues, Filipe Vilas-Boas, Gabriel G Martins, Ana Bagulho, Carla Real
Tumor angiogenesis is required for tumor development and growth and is regulated by several factors including reactive oxygen species (ROS). Hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) is a ROS with an important role in cell signaling but how H<sub>2</sub>O<sub>2</sub> regulates tumor angiogenesis is still poorly understood. We have xenografted tumor cells with altered levels of H<sub>2</sub>O<sub>2</sub> by catalase overexpression into zebrafish embryos to study redox-induced tumor neovascularization...
August 17, 2017: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
https://www.readbyqxmd.com/read/28817646/genetic-dissection-of-endothelial-transcriptional-activity-of-zebrafish-aryl-hydrocarbon-receptors-ahrs
#13
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/28811218/wnt-signaling-positively-regulates-endothelial-cell-fate-specification-in-the-fli1a-positive-progenitor-population-via-lef1
#14
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
#15
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 21, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28774574/fluoro-and-pentafluorothio-analogs-of-the-antitumoral-curcuminoid-ef24-with-superior-antiangiogenic-and-vascular-disruptive-effects
#16
Florian Schmitt, Madeleine Gold, Gerrit Begemann, Ion Andronache, Bernhard Biersack, Rainer Schobert
A series of 14 analogs of the curcuminoid EF24, (3E,5E)-3,5-bis[(2-fluorophenyl)methylene]-4-piperidinone, bearing fluorine or pentafluorothio substituents, were prepared and tested for antiproliferative, vascular-disruptive, and antiangiogenic activity, as well as for their influence on other cancer-relevant targets. They proved antiproliferative against eight cancer cell lines with IC50 values in the low single-digit micromolar to triple-digit nanomolar range. Like EF24, the hexafluoro 3c and 3d and bis(pentafluorothio) 4f derivatives arrested HT-29 colon carcinoma cells in G2/M phase of the cell cycle, yet inhibited angiogenesis, e...
July 21, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28771210/coral-derived-natural-marine-compound-gb9-impairs-vascular-development-in-zebrafish
#17
Yi-Chun Song, Bao-Jueng Wu, Chien-Chih Chiu, Chun-Lin Chen, Jun-Qing Zhou, Shuo-Rong Liang, Chang-Yih Duh, Ping-Jyun Sung, Zhi-Hong Wen, Chang-Yi Wu
Blood vessels in vertebrates are established and genetically controlled in an evolutionarily-conserved manner during embryogenesis. Disruption of vascular growth by chemical compounds or environmental hormones may cause developmental defects. This study analyzed the vascular impacts of marine compound GB9 in zebrafish. GB9 was isolated from the marine soft coral Capnella imbricata and had shown anti-neuroinflammatory and anti-nociceptive activities. However, the role of GB9 on vascular development has not been reported...
August 3, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28762754/flow-responsive-vegfr-pkc%C3%A9-signaling-mediates-glycolytic-metabolites-for-vascular-repair
#18
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/28736676/label-free-photoacoustic-imaging-of-the-cardio-cerebrovascular-development-in-the-embryonic-zebrafish
#19
Qian Chen, Tian Jin, Weizhi Qi, Xianming Mo, Lei Xi
Zebrafish play an important role in biology, pharmacology, toxicology, and medicine. The cardio-cerebrovascular development of zebrafish is particularly critical to understand both brain disorders and cardiovascular diseases in human. In this paper, we applied optical resolution photoacoustic microscopy (ORPAM) to image the whole-body vasculature of the embryonic zebrafish with a special focus on the development of the cardio-cerebrovascular system. Using the intrinsic optical absorption contrast of the embryo, we successfully visualized the formation of the cardio-cerebrovascular network in high-resolution using a 10 × objective, and monitored the whole-body vascular development using a 4 × objective...
April 1, 2017: Biomedical Optics Express
https://www.readbyqxmd.com/read/28723572/robust-identification-of-developmentally-active-endothelial-enhancers-in-zebrafish-using-fans-assisted-atac-seq
#20
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
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