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https://www.readbyqxmd.com/read/29238372/transplantation-of-rat-mesenchymal-stem-cells-overexpressing-hypoxia-inducible-factor-2%C3%AE-improves-blood-perfusion-and-arteriogenesis-in-a-rat-hindlimb-ischemia-model
#1
Weifeng Lu, Xiaoli Chen, Yi Si, Shichai Hong, Zhengyu Shi, Weiguo Fu
Mesenchymal stem cells (MSCs) have been increasingly tested in cell-based therapy to treat numerous diseases. Genetic modification to improve MSC behavior may enhance posttransplantation outcome. This study aims to test the potential therapeutic benefits of rat bone marrow MSCs overexpressing hypoxia-inducible factor 2α (rMSCsHIF-2α ) in a rat hindlimb ischemia model. PBS, rMSCs, or rMSCsHIF-2α were injected into rat ischemic hindlimb. Compared with the injection of PBS or rMSCs, transplantation of rMSCsHIF-2α significantly improved blood perfusion, increased the number of vessel branches in the muscle of the ischemic hindlimb, and improved the foot mobility of the ischemic hindlimb (all P < 0...
2017: Stem Cells International
https://www.readbyqxmd.com/read/29237157/hypoxia-accelerates-aggressiveness-of-hepatocellular-carcinoma-cells-involving-oxidative-stress-epithelial-mesenchymal-transition-and-non-canonical-hedgehog-signaling
#2
Zhikui Liu, Kangsheng Tu, Yufeng Wang, Bowen Yao, Qing Li, Liang Wang, Changwei Dou, Qingguang Liu, Xin Zheng
BACKGROUND/AIMS: Hypoxic microenvironment, a common feature of hepatocellular carcinoma (HCC), can induce HIF-1α expression and promote the epithelial-mesenchymal transition (EMT) and invasion of cancer cells. However, the underlying molecular mechanisms have not fully elucidated. METHODS: HCC cells were cultured under controlled hypoxia conditions or normoxic conditions. Transwell assays were used to examine the migration and invasion capacity. HIF-1α siRNA, cyclopamine (a SMO antagonist) and GLI1 siRNA were used to inhibit HIF-1α transcription or Hh signaling activation...
December 11, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29236166/correction-to-expression-of-matrix-metalloproteinase-12-is-highly-specific-for-non-proliferating-invasive-trophoblasts-in-the-first-trimester-and-temporally-regulated-by-oxygen-dependent-mechanisms-including-hif-1a
#3
Ursula Hiden, Christian P Eyth, Alejandro Majali-Martinez, Gernot Desoye, Carmen Tam-Amersdorfer, Berthold Huppertz, Nassim Ghaffari Tabrizi-Wizsy
In the original publication, the contribution of Dr. Christian Eyth as equal first author was not indicated. This has been corrected confirming that U. Hidden and C. Eyth contributed equally to this work.
December 13, 2017: Histochemistry and Cell Biology
https://www.readbyqxmd.com/read/29235571/the-hypoxia-marker-caix-is-prognostic-in-the-uk-phase-iii-vortex-biobank-cohort-an-important-resource-for-translational-research-in-soft-tissue-sarcoma
#4
Laura Forker, Piers Gaunt, Stefano Sioletic, Patrick Shenjere, Robert Potter, Darren Roberts, Joely Irlam, Helen Valentine, David Hughes, Ana Hughes, Lucinda Billingham, Rob Grimer, Beatrice Seddon, Ananya Choudhury, Martin Robinson, Catharine M L West
BACKGROUND: Despite high metastasis rates, adjuvant/neoadjuvant systemic therapy for localised soft tissue sarcoma (STS) is not used routinely. Progress requires tailoring therapy to features of tumour biology, which need exploration in well-documented cohorts. Hypoxia has been linked to metastasis in STS and is targetable. This study evaluated hypoxia prognostic markers in the phase III adjuvant radiotherapy VorteX trial. METHODS: Formalin-fixed paraffin-embedded tumour biopsies, fresh tumour/normal tissue and blood were collected before radiotherapy...
December 12, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/29233858/enhancement-of-glycolysis-by-inhibition-of-oxygen-sensing-prolyl-hydroxylases-protects-alveolar-epithelial-cells-from-acute-lung-injury
#5
Kentaro Tojo, Nao Tamada, Yusuke Nagamine, Takuya Yazawa, Shuhei Ota, Takahisa Goto
Cellular bioenergetic failure caused by mitochondrial dysfunction is a key process of alveolar epithelial injury during acute respiratory distress syndrome (ARDS). Prolyl hydroxylases (PHDs) act as cellular oxygen sensors, and their inhibition activates hypoxia-inducible factor (HIF), resulting in enhanced cellular glycolytic activity, which could compensate for impaired mitochondrial function and protect alveolar epithelial cells from ARDS. Here, we evaluated the effects of pharmacological PHD inhibition with dimethyloxalylglycine (DMOG) on alveolar epithelial cell injury using in vitro and in vivo ARDS models...
December 12, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29230983/-the-changes-of-hif-1%C3%AE-and-vegf-a-in-myocardial-tissue-of-rats-with-arrhythmias
#6
Y Zhang, Z P Cao, R M Mao, Z B Du, L Mi, X Y Luo, M H Tian, B L Zhu
OBJECTIVES: To observe the expression changes of hypoxia inducible factor-1α(HIF-1α) and vascular endothelial growth factor-A (VEGF-A) in rats with arrhythmias, and to explore the differences of the expression pattern in the two indicators of acute myocardial ischemia caused by arrhythmias and coronary insufficiency. METHODS: The arrhythmia was induced by CaCl₂, and the expression changes of HIF-1α and VEGF-A were detected by immunohistochemistry, Western blotting and real-time PCR within 6 h after the arrhythmia in rats...
June 2017: Fa Yi Xue za Zhi
https://www.readbyqxmd.com/read/29230415/hypoxia-induces-apoptosis-through-hif-1%C3%AE-signaling-pathway-in-human-uterosacral-ligaments-of-pelvic-organ-prolapse
#7
Xinrui Zhao, Congcong Ma, Rui Li, Jing Xue, Lidong Liu, Peishu Liu
The purpose of this study is to evaluate the expression of hypoxia-inducible factor-1α (HIF-1α) in women uterosacral ligament tissues with pelvic organ prolapse and women with normal uterine support structures and illuminate its relationship with apoptosis. Samples were collected from 38 women with pelvic organ prolapse and 31 age matched controls. The expression levels of HIF-1α and BNIP3 in the uterosacral ligaments were measured using immunohistochemistry, qRT-PCR, and Western blot. To assess apoptosis we performed TUNEL assay and Western blot analyses...
2017: BioMed Research International
https://www.readbyqxmd.com/read/29230384/non-canonical-mechanisms-regulating-hypoxia-inducible-factor-1-alpha-in-cancer
#8
REVIEW
Luisa Iommarini, Anna Maria Porcelli, Giuseppe Gasparre, Ivana Kurelac
Hypoxia-inducible factor 1 alpha (HIF-1α) orchestrates cellular adaptation to low oxygen and nutrient-deprived environment and drives progression to malignancy in human solid cancers. Its canonical regulation involves prolyl hydroxylases (PHDs), which in normoxia induce degradation, whereas in hypoxia allow stabilization of HIF-1α. However, in certain circumstances, HIF-1α regulation goes beyond the actual external oxygen levels and involves PHD-independent mechanisms. Here, we gather and discuss the evidence on the non-canonical HIF-1α regulation, focusing in particular on the consequences of mitochondrial respiratory complexes damage on stabilization of this pleiotropic transcription factor...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/29230182/a-network-model-to-explore-the-effect-of-the-micro-environment-on-endothelial-cell-behavior-during-angiogenesis
#9
Nathan Weinstein, Luis Mendoza, Isidoro Gitler, Jaime Klapp
Angiogenesis is an important adaptation mechanism of the blood vessels to the changing requirements of the body during development, aging, and wound healing. Angiogenesis allows existing blood vessels to form new connections or to reabsorb existing ones. Blood vessels are composed of a layer of endothelial cells (ECs) covered by one or more layers of mural cells (smooth muscle cells or pericytes). We constructed a computational Boolean model of the molecular regulatory network involved in the control of angiogenesis...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/29230103/oxygen-supplementation-ameliorates-tibial-development-via-stimulating-vascularization-in-tibetan-chickens-at-high-altitudes
#10
Shucheng Huang, Xiaole Tong, Mujeeb Ur Rehman, Meng Wang, Lihong Zhang, Lei Wang, Jiakui Li, Shijin Yang
Tibetan chickens (TBCs) living in high-altitude hypoxic environment, are characterized by delayed growth and small size as compared to low-altitude broiler chickens. Increasing evidences signify the beneficial effect of oxygen (O2) supplementation in animal's body for regulating their body growth and organ development. However, it is still unclear that whether O2 supplementation has an ameliorative and protective role in TBCs living at high altitude. In this study, we first found that O2 supplementation not only increased the survival rate but also promoted the growth of TBCs associated with bone development...
2017: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/29228704/role-of-hif-1a-in-regulating-autophagic-cell-survival-during-cerebral-ischemia-reperfusion-in-rats
#11
Yongqing Guo
Hypoxia-inducible factor-1a (HIF-1a) plays a beneficial role during cerebral ischemia reperfusion (IR), but the underlying molecular mechanisms are not completely understood. Here, we aimed to investigate the effects and molecular regulation of HIF-1a on brain cell apoptosis and autophagy during IR. We found that augmentation of HIF-1a in re-perfused hematopoietic cells significantly reduced brain damage, alleviated brain edema and improved neural function during IR, seemingly through two HIF-1a target genes BNIP3 and NIX, which were critical regulators for cell apoptosis and autophagic cell survival...
November 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29227282/hypoxia-induced-upregulation-of-bmx-kinase-mediates-therapeutic-resistance-in-acute-myeloid-leukemia
#12
Jolieke G van Oosterwijk, Daelynn R Buelow, Christina D Drenberg, Aksana Vasilyeva, Lie Li, Lei Shi, Yong-Dong Wang, David Finkelstein, Sheila A Shurtleff, Laura J Janke, Stanley Pounds, Jeffrey E Rubnitz, Hiroto Inaba, Navjotsingh Pabla, Sharyn D Baker
Oncogenic addiction to the Fms-like tyrosine kinase 3 (FLT3) is a hallmark of acute myeloid leukemia (AML) that harbors the FLT3-internal tandem duplication (FLT3-ITD) mutation. While FLT3 inhibitors like sorafenib show initial therapeutic efficacy, resistance rapidly develops through mechanisms that are incompletely understood. Here, we used RNA-Seq-based analysis of patient leukemic cells and found that upregulation of the Tec family kinase BMX occurs during sorafenib resistance. This upregulation was recapitulated in an in vivo murine FLT3-ITD-positive (FLT3-ITD+) model of sorafenib resistance...
December 11, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29225432/molecular-docking-based-screening-of-a-simulated-hif-1-protein-model-for-potential-inhibitors
#13
Mundla Sri Latha, Madhu Sudhana Saddala
Hypoxia inducible factor-1(HIF-1) is a bHLH-family transcription factor that control genes involved in glucolysis, angiogenesis, migration, as well as invasion factors that are important for tumor progression and metastasis. HIF-1, a hetero dimer of HIF-1α and HIF-1β, binds to the hypoxia responsive genes, such as vascular endothelial growth factor (VEGF). It is one the molecular target for angiogenesis. A series of Chalcone - like compounds described that preferentially inhibit HIF-1 dimer, which can interact with amino acids within the active site of the protein...
2017: Bioinformation
https://www.readbyqxmd.com/read/29223764/hypoxia-induced-and-hif1%C3%AE-vegf-mediated-tight-junction-dysfunction-in-choriocarcinoma-cells-implications-for-preeclampsia
#14
Yuan Zhang, Hai-Jun Zhao, Xin-Ru Xia, Fei-Yang Diao, Xiang Ma, Jing Wang, Li Gao, Jie Liu, Chao Gao, Yu-Gui Cui, Jia-Yin Liu
INTRODUCTION: Accumulated data indicate that placental hypoxia is implicated in the pathogenesis of preeclampsia (PE). Tight junction (TJ) is important structure that sustains normal placental barrier function, its dysregulation under hypoxia has been observed. This study was designed to explore hypoxia-induced TJ dysfunction in trophoblast cells and its possible involvement in PE pathophysiology. METHODS: Choriocarcinoma cells were grown in a monolayer and treated with cobalt chloride (CoCl2) to induce hypoxia...
December 6, 2017: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/29222481/hypoxia-inducible-factor-prolyl-4-hydroxylase-1-is-a-convergent-point-in-the-reciprocal-negative-regulation-of-nf-%C3%AE%C2%BAb-and-p53-signaling-pathways
#15
Karim Ullah, Ann-Helen Rosendahl, Valerio Izzi, Ulrich Bergmann, Taina Pihlajaniemi, Joni M Mäki, Johanna Myllyharju
Hypoxia-inducible factor 1α (HIF1α) induces the expression of several hundred genes in hypoxia aiming at restoration of oxygen homeostasis. HIF prolyl-4-hydroxylases (HIF-P4Hs) regulate the stability of HIF1α in an oxygen-dependent manner. Hypoxia is a common feature in inflammation and cancer and the HIF pathway is closely linked with the inflammatory NF-κB and tumor suppressor p53 pathways. Here we show that genetic inactivation or chemical inhibition of HIF-P4H-1 leads to downregulation of proinflammatory genes, while proapoptotic genes are upregulated...
December 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29222473/hypoxia-inducible-factor-1%C3%AE-is-essential-for-macrophage-mediated-erythroblast-proliferation-in-acute-friend-retrovirus-infection
#16
Timm Schreiber, Theresa Quinting, Ulf Dittmer, Joachim Fandrey, Kathrin Sutter
Macrophages are the frontline of defence against foreign microorganisms, including bacteria, parasites, and viruses. During acute viral infection, macrophages must invade the inflamed tissue toward low oxygen concentrations, where genetic cellular responses depend on hypoxia-inducible factors (HIF). In the study reported here we investigated the role of HIF-1α in macrophage function during acute retroviral infection. Wild-type and myeloid cell-specific HIF-1α knockout mice were infected with Friend retrovirus (FV), and immune response was analysed 7 and 10 days after infection...
December 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29222329/glutaminolysis-is-required-for-tgf-%C3%AE-1-induced-myofibroblast-differentiation-and-activation
#17
Karen Bernard, Naomi J Logsdon, Gloria A Benavides, Yan Sanders, Jianhua Zhang, Victor M Darley-Usmar, Victor J Thannickal
Myofibroblasts participate in physiological wound healing and pathological fibrosis.  Myofibroblast differentiation is characterized by the expression of alpha-smooth muscle actin (α-SMA) and extracellular matrix (ECM) proteins, and is dependent on metabolic reprogramming.  In this study, we explored the role of glutaminolysis and metabolites of the tricarboxylic acid cycle (TCA) in supporting myofibroblast differentiation.  Glutaminolysis converts glutamine (Gln) into alpha-ketoglutarate (α-KG), a critical intermediate in the TCA cycle...
December 8, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29219948/asperosaponin-vi-promotes-angiogenesis-and-accelerates-wound-healing-in-rats-via-up-regulating-hif-1%C3%AE-vegf-signaling
#18
Cheng-Gui Wang, Yi-Ting Lou, Min-Ji Tong, Li-Lian Zhang, Zeng-Jie Zhang, Yong-Zeng Feng, Shi Li, Hua-Zi Xu, Cong Mao
Wound therapy remains a clinical challenge due to the complexity of healing pathology and high demand of achieving functional and aesthetically satisfactory scars. Newly formed blood vessels are essential for tissue repair since they can support cells at the wound site with nutrition and oxygen. In this study, we investigated the effects of Asperosaponin VI (ASA VI) isolated from a traditional Chinese medicine, the root of Dipsacus asper Wall, in promoting angiogenesis, as well as its function in wound therapeutics...
December 7, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/29216640/celecoxib-down-regulates-the-hypoxia-induced-expression-of-hif-1%C3%AE-and-vegf-through-the-pi3k-akt-pathway-in-retinal-pigment-epithelial-cells
#19
Yi-Zhou Sun, Na Cai, Ning-Ning Liu
BACKGROUND/AIMS: The goal of this study was to detect the expression of hypoxia-inducible factor 1α (HIF-1α) and vascular endothelial growth factor (VEGF) in human retinal pigmented epithelial (RPE) cells treated with celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, under hypoxic and normoxic conditions and to explore the signaling mechanism involved in regulating the hypoxia-induced expression of HIF-1α and VEGF in RPE cells. METHODS: D407 cells were cultured in normoxic or hypoxic conditions, with or without celecoxib or a PI3K inhibitor (LY294002)...
December 6, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29212519/gper-mediates-the-angiocrine-actions-induced-by-igf1-through-the-hif-1%C3%AE-vegf-pathway-in-the-breast-tumor-microenvironment
#20
Ernestina M De Francesco, Andrew H Sims, Marcello Maggiolini, Federica Sotgia, Michael P Lisanti, Robert B Clarke
BACKGROUND: The G protein estrogen receptor GPER/GPR30 mediates estrogen action in breast cancer cells as well as in breast cancer-associated fibroblasts (CAFs), which are key components of microenvironment driving tumor progression. GPER is a transcriptional target of hypoxia inducible factor 1 alpha (HIF-1α) and activates VEGF expression and angiogenesis in hypoxic breast tumor microenvironment. Furthermore, IGF1/IGF1R signaling, which has angiogenic effects, has been shown to activate GPER in breast cancer cells...
December 6, 2017: Breast Cancer Research: BCR
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