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https://www.readbyqxmd.com/read/28060188/prox1-gene-cc-genotype-as-a-major-determinant-of-early-onset-of-type-2-diabetes-in-slavic-study-participants-from-action-in-diabetes-and-vascular-disease-preterax-and-diamicron-mr-controlled-evaluation-study
#1
Pavel Hamet, Mounsif Haloui, François Harvey, François-Christophe Marois-Blanchet, Marie-Pierre Sylvestre, Muhammad-Ramzan Tahir, Paul H G Simon, Beatriz Sonja Kanzki, John Raelson, Carole Long, John Chalmers, Mark Woodward, Michel Marre, Stephen Harrap, Johanne Tremblay
BACKGROUND: The prevalence of diabetic nephropathy varies according to ethnicity. Environmental as well as genetic factors contribute to the heterogeneity in the presentation of diabetic nephropathy. Our objective was to evaluate this heterogeneity within the Caucasian population. METHODS: The geo-ethnic origin of the 3409 genotyped Caucasian type 2 diabetes (T2D) patients of Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation was determined using principal component analysis...
January 5, 2017: Journal of Hypertension
https://www.readbyqxmd.com/read/28055225/overexpression-of-prox1-induces-the-differentiation-of-human-adipose-derived-stem-cells-into-lymphatic-endothelial-like-cells-in-vitro
#2
Jingcheng Deng, Tingting Dai, Yiyu Sun, Qi Zhang, Zhaohua Jiang, Shengli Li, Weigang Cao
Constant levels of homeobox transcription factor Prox1 expression are required throughout the life of lymphatic endothelial cells (LECs) to maintain their differentiated identity. Recent studies have demonstrated that using human LECs for cell transplantation therapy may improve secondary lymphedema in a nude rat model. However, the application is currently limited by the low yield of LECs. In this study, Prox1 was overexpressed in human adipose tissue-derived stem cells (hADSCs) by using the transfection of lentiviral vectors to induce the differentiation of hADSCs to LECs...
January 5, 2017: Cellular Reprogramming
https://www.readbyqxmd.com/read/28035380/prox1-promotes-human-glioblastoma-cell-proliferation-and-invasion-via-activation-of-the-nuclear-factor-%C3%AE%C2%BAb-signaling-pathway
#3
Xuchang Xu, Xuefeng Wan, Xinting Wei
Prospero homeobox protein 1 (PROX1) is highly expressed in high-grade malignant astrocytic gliomas. However, the role of PROX1 in the pathogenesis of glioblastoma multiforme (GBM) remains unclear. The present study overexpressed PROX1 in human GBM cell lines and examined its effects on cell growth, tumorigenesis, and invasiveness. In addition, the involvement of the nuclear factor‑κB (NF‑κB) signaling pathway in the action of PROX1 was examined. It was identified that overexpression of PROX1 significantly increased the proliferation and colony formation of glioblastoma cells, compared with empty vector‑transfected controls...
December 27, 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28026853/lyve1-and-prox1-in-the-reconstruction-of-hepatic-sinusoids-after-partial-hepatectomy-in-mice
#4
Fanwei Meng
Revascularization is crucial to liver regeneration after liver injury, but the process remains unclear. This study investigated changes in the levels and distribution of lymphatic vessel endothelial hyaluronan receptor 1 (LYVE1) and prospero homeobox protein 1 (PROX1) in liver tissue sections after partial hepatectomy in mice. Mice were subjected to partial hepatectomy. Control animals were sham-operated. From days 1 through 8, the remaining liver tissues were collected from 8 animals each day. Histology showed that after partial hepatectomy, the remaining liver tissue samples underwent initial degeneration and then hepatocyte proliferation and regeneration...
December 27, 2016: Folia Morphologica (Warsz)
https://www.readbyqxmd.com/read/28024299/the-role-of-fatty-acid-%C3%AE-oxidation-in-lymphangiogenesis
#5
Brian W Wong, Xingwu Wang, Annalisa Zecchin, Bernard Thienpont, Ivo Cornelissen, Joanna Kalucka, Melissa García-Caballero, Rindert Missiaen, Hongling Huang, Ulrike Brüning, Silvia Blacher, Stefan Vinckier, Jermaine Goveia, Marlen Knobloch, Hui Zhao, Cathrin Dierkes, Chenyan Shi, René Hägerling, Veronica Moral-Dardé, Sabine Wyns, Martin Lippens, Sebastian Jessberger, Sarah-Maria Fendt, Aernout Luttun, Agnès Noel, Friedemann Kiefer, Bart Ghesquière, Lieve Moons, Luc Schoonjans, Mieke Dewerchin, Guy Eelen, Diether Lambrechts, Peter Carmeliet
Lymphatic vessels are lined by lymphatic endothelial cells (LECs), and are critical for health. However, the role of metabolism in lymphatic development has not yet been elucidated. Here we report that in transgenic mouse models, LEC-specific loss of CPT1A, a rate-controlling enzyme in fatty acid β-oxidation, impairs lymphatic development. LECs use fatty acid β-oxidation to proliferate and for epigenetic regulation of lymphatic marker expression during LEC differentiation. Mechanistically, the transcription factor PROX1 upregulates CPT1A expression, which increases acetyl coenzyme A production dependent on fatty acid β-oxidation...
December 26, 2016: Nature
https://www.readbyqxmd.com/read/28013212/organ-specific-epigenetic-changes-induced-by-the-non-genotoxic-liver-carcinogen-methapyrilene-in-fischer-344-rats
#6
Svitlana Shpyleva, Kostiantyn Dreval, Aline de Conti, Iryna Kindrat, Stepan Melnyk, Jian Yan, Tao Chen, Frederick A Beland, Igor P Pogribny
Continuous lifetime exposure to certain natural and man-made chemicals is a major cause of cancers in humans; therefore, evaluating the carcinogenic risks of chemicals remains important. Currently, substantial progress has been made in identification of genotoxic carcinogens; in contrast, predicting a carcinogenic potential of non-genotoxic compounds is a challenge due to many different modes of action that may lead to tumorigenesis. In the present study, we investigated the effects of the non-genotoxic liver carcinogen methapyrilene and the nongenotoxic non-carcinogen usnic acid at doses that do not exhibit organ cytotoxicity on epigenomic alterations in the liver and kidneys of Fischer 344 (F344) rats...
December 24, 2016: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28012947/the-gsk-3-inhibitor-vp2-51-produces-antidepressant-effects-associated-with-adult-hippocampal-neurogenesis
#7
Paloma Pérez-Domper, Valle Palomo, Simona Gradari, Carmen Gil, María L de Ceballos, Ana Martínez, Jose Luis Trejo
Glycogen synthase kinase 3 (GSK-3) is a constitutively active kinase that has been implicated in the mechanism of action of mood stabilizers. According to the neurogenic hypothesis of depression, newborn neurons in the adult dentate gyrus are required for the antidepressant effects of certain agents. We demonstrate that administration of the GSK-3 inhibitor VP2.51 (2.5 mg/kg ip, for 3.5 weeks) increases cell proliferation (pH3(+) cells), as well as the short- and long-term survival of newborn neurons (assessed by the 24 h survival of BrdU(+) and DCX(+) neurons), while significantly increasing the commitment of cells to the granule neuron lineage (Prox1 immunoreactivity)...
December 22, 2016: Neuropharmacology
https://www.readbyqxmd.com/read/27928788/-basic-and-translational-research-progress-of-gastrointestinal-neuroendocrine-neoplasmas
#8
Yuli Song, Xiaoyi Li, Tiantian Song, Guole Lin, Yuanjia Chen
Gastrointestinal neuroendocrine tumors are a group of highly heterogeneous tumors. Their incidences have increased in the Western countries as well as in Asia for years. In recent years, predominant progression has been made in the basic and translational studies on gastrointestinal neuroendocrine tumors. Gastric neuroendocrine neoplasmas are classified as four types: type I( occurs on the basis of autoimmune atrophic gastritis, type II( clinically manifests as multiple endocrine tumor type I( and Zollinger-Ellison syndrome, type III( is sporadic neuroendocrine neoplasmas, and type IIII( is neuroendocrine carcinoma...
November 25, 2016: Zhonghua Wei Chang Wai Ke za Zhi, Chinese Journal of Gastrointestinal Surgery
https://www.readbyqxmd.com/read/27916465/hypoxia-inhibits-lymphatic-thoracic-duct-formation-in-zebrafish
#9
Isabelle Ernens, Andrew I Lumley, Lu Zhang, Yvan Devaux, Daniel R Wagner
Hypoxia promotes blood vessel growth through up-regulation of pro-angiogenic pathways but its role on the lymphatic system remains unclear. The homeobox transcription factor Prox1 is a master control gene for generating lymphatic endothelial cells (LECs) and is up-regulated by hypoxia-inducible factors in mammals. While vascular endothelial growth factor A (VEGFA) is critical for angiogenesis, VEGFC and its receptor VEGF receptor-3 (VEGFR-3) are essential for the initial sprouting and directed migration as well as for the subsequent survival of LECs...
January 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27873085/quantitative-analysis-of-supporting-cell-subtype-labeling-among-creer-lines-in-the-neonatal-mouse-cochlea
#10
Melissa M McGovern, Joseph Brancheck, Auston C Grant, Kaley A Graves, Brandon C Cox
Four CreER lines that are commonly used in the auditory field to label cochlear supporting cells (SCs) are expressed in multiple SC subtypes, with some lines also showing reporter expression in hair cells (HCs). We hypothesized that altering the tamoxifen dose would modify CreER expression and target subsets of SCs. We also used two different reporter lines, ROSA26 (tdTomato) and CAG-eGFP, to achieve the same goal. Our results confirm previous reports that Sox2 (CreERT2) and Fgfr3-iCreER (T2) are not only expressed in neonatal SCs but also in HCs...
November 21, 2016: Journal of the Association for Research in Otolaryngology: JARO
https://www.readbyqxmd.com/read/27845051/intrinsic-lens-potential-of-neural-retina-inhibited-by-notch-signaling-as-the-cause-of-lens-transdifferentiation
#11
Hideaki Iida, Yasuo Ishii, Hisato Kondoh
Embryonic neural retinas of avians produce lenses under spreading culture conditions. This phenomenon has been regarded as a paradigm of transdifferentiation due to the overt change in cell type. Here we elucidated the underlying mechanisms. Retina-to-lens transdifferentiation occurs in spreading cultures, suggesting that it is triggered by altered cell-cell interactions. Thus, we tested the involvement of Notch signaling based on its role in retinal neurogenesis. Starting from E8 retina, a small number of crystallin-expressing lens cells began to develop after 20 days in control spreading cultures...
January 15, 2017: Developmental Biology
https://www.readbyqxmd.com/read/27826002/3d-culture-of-human-pluripotent-stem-cells-in-rgd-alginate-hydrogel-improves-retinal-tissue-development
#12
Nicola C Hunt, Dean Hallam, Ayesha Karimi, Carla B Mellough, Jinju Chen, David H W Steel, Majlinda Lako
: No treatments exist to effectively treat many retinal diseases. Retinal pigmented epithelium (RPE) and neural retina can be generated from human embryonic stem cells/induced pluripotent stem cells (hESCs/hiPSCs). The efficacy of current protocols is, however, limited. It was hypothesised that generation of laminated neural retina and/or RPE from hiPSCs/hESCs could be enhanced by three dimensional (3D) culture in hydrogels. hiPSC- and hESC-derived embryoid bodies (EBs) were encapsulated in 0...
November 5, 2016: Acta Biomaterialia
https://www.readbyqxmd.com/read/27810495/psoriasis-risk-snps-and-their-association-with-hiv-1-control
#13
Joanne Nititham, Rashmi Gupta, Xue Zeng, Wendy Hartogensis, Douglas F Nixon, Steven G Deeks, Frederick M Hecht, Wilson Liao
Human evolution has resulted in selection for genetic polymorphisms beneficial in the defense against pathogens. However, such polymorphisms may have the potential to heighten the risk of autoimmune disease. Here, we investigated whether psoriasis-associated single nucleotide polymorphisms influence host control of HIV-1 infection. We studied psoriasis and viral immune response variants in three HIV-positive cohorts: (1) HIV-1 controllers and non-controllers in the Study of the Consequences of the Protease Inhibitor Era (SCOPE) cohort (n=366), (2) Individuals with primary HIV infection in the Options cohort (n=675), and (3) HIV-positive injection drug users from the Urban Health Study (UHS) (n=987)...
October 31, 2016: Human Immunology
https://www.readbyqxmd.com/read/27800509/hyperplasia-and-hypertrophy-of-pulmonary-neuroepithelial-bodies-presumed-airway-hypoxia-sensors-in-hypoxia-inducible-factor-prolyl-hydroxylase-deficient-mice
#14
Jie Pan, Tammie Bishop, Peter J Ratcliffe, Herman Yeger, Ernest Cutz
Pulmonary neuroepithelial bodies (NEBs), presumed polymodal airway sensors, consist of innervated clusters of amine (serotonin) and peptide-producing cells. While NEB responses to acute hypoxia are mediated by a membrane-bound O2 sensor complex, responses to sustained and/or chronic hypoxia involve a prolyl hydroxylase (PHD)-hypoxia-inducible factor-dependent mechanism. We have previously reported hyperplasia of NEBs in the lungs of Phd1-/- mice associated with enhanced serotonin secretion. Here we use a novel multilabel immunofluorescence method to assess NEB distribution, frequency, and size, together with the number and size of NEB cell nuclei, and to colocalize multiple cytoplasmic and nuclear epitopes in the lungs of Phd1-/-, Phd2+/-, and Phd3-/- mice and compare them with wild-type controls...
2016: Hypoxia
https://www.readbyqxmd.com/read/27753926/os-05-01-prox1-gene-cc-genotype-as-a-major-determinant-of-early-onset-of-t2d-and-cardiovascular-complications-in-slavic-subjects-from-advance-study
#15
Pavel Hamet, Mounsif Haloui, François Harvey, François-Christophe Marois-Blanchet, Paul Simon, John Raelson, Michael Phillips, John Chalmers, Mark Woodward, Michel Marre, Stephen Harrap, Johanne Tremblay
OBJECTIVE: We have previously reported distinct genetic architectures of renal impairment in T2D patients of Slavic and Celtic origins participating in the ADVANCE trial (J Hypertens. 2015 Jun;33 Suppl 1:e3). Further analysis suggests that the major driver of the difference in the prevalence of T2D complications between Slavic and Celtic groups is due to an earlier onset of diabetes in Slavic patients. In an attempt to distinguish between environmental and genetic factors on age of onset of diabetes, we have determined the age of onset of T2D in Slavic subjects living in Celtic countries and confirmed the same earlier onset (-2 years) in these subjects, notwithstanding their living environment...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27731315/the-transcription-factor-prox1-is-essential-for-satellite-cell-differentiation-and-muscle-fibre-type-regulation
#16
Riikka Kivelä, Ida Salmela, Yen Hoang Nguyen, Tatiana V Petrova, Heikki A Koistinen, Zoltan Wiener, Kari Alitalo
The remarkable adaptive and regenerative capacity of skeletal muscle is regulated by several transcription factors and pathways. Here we show that the transcription factor Prox1 is an important regulator of myoblast differentiation and of slow muscle fibre type. In both rodent and human skeletal muscles Prox1 is specifically expressed in slow muscle fibres and in muscle stem cells called satellite cells. Prox1 activates the NFAT signalling pathway and is necessary and sufficient for the maintenance of the gene program of slow muscle fibre type...
October 12, 2016: Nature Communications
https://www.readbyqxmd.com/read/27725907/mir-489-acts-as-a-tumor-suppressor-in-human-gastric-cancer-by-targeting-prox1
#17
Bin Zhang, Sheqing Ji, Fei Ma, Qi Ma, Xianzhi Lu, Xiaobing Chen
Dysregulation of microRNAs (miRNAs) are linked to tumorigenesis and tumor progression. In this study, we examined the expression of miR-489 in gastric cancer tissues and cells. Loss- and gain-of-function experiments were done to determine the roles of miR-489 in gastric cancer cell proliferation and invasion. Bioinformatic prediction, luciferase reporter assays, and Western blot analysis were employed to identify the target gene(s) of miR-489. We found that miR-489 was significantly (P < 0.05) downregulated in human gastric cancer tissues and cell lines, compared to their non-malignant counterparts...
2016: American Journal of Cancer Research
https://www.readbyqxmd.com/read/27684496/hematopoietically-expressed-homeobox-hhex-gene-polymorphism-rs5015480-is-associated-with-increased-risk-of-gestational-diabetes-mellitus
#18
M Tarnowski, D Malinowski, K Safranow, V Dziedziejko, M Czerewaty, A Pawlik
Gestational diabetes mellitus (GDM) is a metabolic disorder that occurs during pregnancy. HHEX and PROX1 are genetic loci associated with diabetes mellitus type 2. HHEX and PROX1 play significant roles in carbohydrate intolerance and diabetes because these transcription factors may be involved in the regulation of insulin secretion and in glucose and lipid metabolism. The aim of this study was to examine the association between HHEX (rs5015480) and PROX1 (rs340874) gene polymorphisms and GDM. This study included 204 pregnant women with GDM and 207 pregnant women with the normal glucose tolerance (NGT)...
September 29, 2016: Clinical Genetics
https://www.readbyqxmd.com/read/27664768/gene-expression-analysis-during-the-induction-and-patterning-of-the-conjunctival-papillae-in-the-chick-embryonic-eye
#19
Karyn Jourdeuil, Tamara Anne Franz-Odendaal
The induction and patterning of the conjunctival papillae (i.e. epithelial thickenings of the conjunctiva required for the induction of the underlying, neural crest-derived scleral ossicles) is complex. It takes place over a period of two days and follows a defined spatiotemporal sequence. In this study, we investigated the spatial and temporal expression pattern of four genes over seven morphological stages of development of these papillae. We show that β-catenin is expressed during the pre-patterning of the epithelium prior to papilla induction and second that β-catenin, Ednrb and Inhba are expressed during the induction and patterning of the conjunctival papillae...
September 2016: Gene Expression Patterns: GEP
https://www.readbyqxmd.com/read/27643319/os-05-01-prox1-gene-cc-genotype-as-a-major-determinant-of-early-onset-of-t2d-and-cardiovascular-complications-in-slavic-subjects-from-advance-study
#20
Pavel Hamet, Mounsif Haloui, François Harvey, François-Christophe Marois-Blanchet, Paul Simon, John Raelson, Michael Phillips, John Chalmers, Mark Woodward, Michel Marre, Stephen Harrap, Johanne Tremblay
OBJECTIVE: We have previously reported distinct genetic architectures of renal impairment in T2D patients of Slavic and Celtic origins participating in the ADVANCE trial (J Hypertens. 2015 Jun;33 Suppl 1:e3). Further analysis suggests that the major driver of the difference in the prevalence of T2D complications between Slavic and Celtic groups is due to an earlier onset of diabetes in Slavic patients. In an attempt to distinguish between environmental and genetic factors on age of onset of diabetes, we have determined the age of onset of T2D in Slavic subjects living in Celtic countries and confirmed the same earlier onset (-2 years) in these subjects, notwithstanding their living environment...
September 2016: Journal of Hypertension
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