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https://www.readbyqxmd.com/read/29924941/therapeutic-targeting-of-vascular-remodeling-and-right-heart-failure-in-pah-with-hif-2%C3%AE-inhibitor
#1
Zhiyu Dai, Maggie M Zhu, Yi Peng, Narsa Machireddy, Colin E Evans, Roberto Machado, Xianming Zhang, You-Yang Zhao
RATIONALE: Pulmonary arterial hypertension (PAH) is a devastating disease characterized by progressive vasoconstriction and obliterative vascular remodeling that leads to right heart failure (RHF) and death. Current therapies do not target vascular remodeling and RHF, and only result in modest improvement of morbidity and mortality. OBJECTIVE: To determine whether targeting HIF-2α with a HIF-2α-selective inhibitor could reverse PAH and RHF in different rodent PAH models...
June 20, 2018: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/29922454/use-of-integrative-epigenetic-and-mrna-expression-analyses-to-identify-significantly-changed-genes-and-functional-pathways-in-osteoarthritic-cartilage
#2
A He, Y Ning, Y Wen, Y Cai, K Xu, Y Cai, J Han, L Liu, Y Du, X Liang, P Li, Q Fan, J Hao, X Wang, X Guo, T Ma, F Zhang
Aim: Osteoarthritis (OA) is caused by complex interactions between genetic and environmental factors. Epigenetic mechanisms control the expression of genes and are likely to regulate the OA transcriptome. We performed integrative genomic analyses to define methylation-gene expression relationships in osteoarthritic cartilage. Patients and Methods: Genome-wide DNA methylation profiling of articular cartilage from five patients with OA of the knee and five healthy controls was conducted using the Illumina Infinium HumanMethylation450 BeadChip (Illumina, San Diego, California)...
May 2018: Bone & Joint Research
https://www.readbyqxmd.com/read/29921553/il-33-initiates-vascular-remodelling-in-hypoxic-pulmonary-hypertension-by-up-regulating-hif-1%C3%AE-and-vegf-expression-in-vascular-endothelial-cells
#3
Jie Liu, Wang Wang, Lei Wang, Shihao Chen, Bo Tian, Kewu Huang, Chris J Corrigan, Sun Ying, Wei Wang, Chen Wang
IL-33 may play a role in the vascular remodelling of hypoxic pulmonary hypertension (PH) but the precise mechanisms are still unclear. We hypothesized that hypoxia promotes expression of IL-33 and its receptor ST2 on vascular endothelial cells, which in turn leads to dysfunction of vascular endothelial cells and smooth muscle cells contributing to PH. Immunohistochemistry showed that immunoreactivity for IL-33 and ST2 was significantly increased in lung tissue of murine model of hypoxia-induced PH (HPH) and of subjects with bronchiectasis-PH...
June 16, 2018: EBioMedicine
https://www.readbyqxmd.com/read/29920371/cysteinyl-leukotriene-pathway-as-a-new-therapeutic-target-for-the-treatment-of-atherosclerosis-related-to-obstructive-sleep-apnea-syndrome
#4
Elodie Gautier-Veyret, Magnus Bäck, Claire Arnaud, Elise Belaïdi, Renaud Tamisier, Patrick Lévy, Nathalie Arnol, Marion Perrin, Jean-Louis Pépin, Françoise Stanke-Labesque
AIMS: Obstructive sleep apnea (OSA) characterized by nocturnal intermittent hypoxia (IH) is associated with atherosclerosis and cysteinyl-leukotrienes (CysLT) pathway activation. We aimed to identify the determinants of CysLT pathway activation and the role of CysLT in OSA-related atherosclerosis. METHODS AND RESULTS: Determinants of the urinary excretion of LTE4 (U-LTE4 ) including history of cardiovascular events, polysomnographic and biological parameters were studied in a cohort of 170 OSA patients and 29 controls, and in a subgroup of OSA patients free of cardiovascular event (n = 136)...
June 16, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29917232/phd2-inactivation-in-type-i-cells-drives-hif-2%C3%AE-dependent-multi-lineage-hyperplasia-and-the-formation-of-paraganglioma-like-carotid-bodies
#5
James W Fielding, Emma J Hodson, Xiaotong Cheng, David J P Ferguson, Luise Eckardt, Julie Adam, Philomena Lip, Matthew Maton-Howarth, Indrika Ratnayaka, Christopher W Pugh, Keith J Buckler, Peter J Ratcliffe, Tammie Bishop
The carotid body is a peripheral chemoreceptor that plays a central role in mammalian oxygen homeostasis. In response to sustained hypoxia, it manifests rapid cellular proliferation and an associated increase in responsiveness to hypoxia. Understanding the cellular and molecular mechanisms underlying these processes is of interest both to specialised chemoreceptive functions of that organ and potentially to the general physiology and pathophysiology of cellular hypoxia. We have combined cell lineage tracing technology and conditionally inactivated alleles in recombinant mice to examine the role of components of the HIF hydroxylase pathway in specific cell types within the carotid body...
June 19, 2018: Journal of Physiology
https://www.readbyqxmd.com/read/29917203/mirna-26a-promotes-angiogenesis-in-a-rat-model-of-cerebral-infarction-via-pi3k-akt-and-mapk-erk-pathway
#6
Z Liang, Y-J Chi, G-Q Lin, S-H Luo, Q-Y Jiang, Y-K Chen
OBJECTIVE: To investigate the specific role of microRNA-26 (miRNA-26a) in a rat model of cerebral ischemic stroke and the underlying mechanism. MATERIALS AND METHODS: A rat model of middle cerebral artery occlusion (MCAO) was established to induce permanent cerebral infarction. Neuro-behavior was observed and scored after model establishment. The expression of miRNA-26a in brain tissue and brain microvascular endothelial cells (BMECs) of rats after cerebral ischemic stroke was detected by quantitative polymerase chain reaction (qPCR)...
June 2018: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29917189/expressions-and-correlation-analysis-of-hif-1%C3%AE-survivin-and-vegf-in-patients-with-hepatocarcinoma
#7
Q-G Tian, Y-T Wu, Y Liu, J Zhang, Z-Q Song, W-F Gao, T-K Guo, C-H He, F-R Dai
OBJECTIVE: To investigate the expressions of HIF-1α, surviving, and VEGF in patients with hepatocarcinoma as well as the correlation analysis among them. PATIENTS AND METHODS: 65 patients, who were admitted to our hospital and diagnosed as hepatocarcinoma from January 2014 to October 2015, were selected as hepatocarcinoma group, while 50 healthy cases that do not have hepatocarcinoma were selected as normal control group. The expression levels of HIF-1α, surviving, and VEGF in hepatocarcinoma tissues of hepatocarcinoma group and normal liver tissues of control group were detected by immunohistochemical (SP) staining method; then, the correlation among them was explored...
June 2018: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29916053/crystallization-from-supersaturated-solutions-role-of-lecithin-and-composite-simulated-intestinal-fluid
#8
Anura S Indulkar, Yi Gao, Shweta A Raina, Geoff G Z Zhang, Lynne S Taylor
PURPOSE: The overall purpose of this study was to understand the impact of different biorelevant media types on solubility and crystallization from supersaturated solutions of model compounds (atazanavir, ritonavir, tacrolimus and cilnidipine). The first aim was to understand the influence of the lecithin content in FaSSIF. As the human intestinal fluids (HIFs) contain a variety of bile salts in addition to sodium taurocholate (STC), the second aim was to understand the role of these bile salts (in the presence of lecithin) on solubility and crystallization from supersaturated solutions, METHODS: To study the impact of lecithin, media with 3 mM STC concentration but varying lecithin concentration were prepared...
June 18, 2018: Pharmaceutical Research
https://www.readbyqxmd.com/read/29914529/letter-to-the-editor-is-hif-1%C3%AE-a-viable-prognostic-indicator-in-oscc-a-critical-review-of-a-meta-analysis-study
#9
Rama Jayaraj, Chellan Kumarasamy, Madhav Madurantakam Royam, Arikketh Devi, Siddharta Baxi
The study performed by Zhou et al. (World J Surg Oncol 15:104, 2017) titled "Clinical and prognostic significance of HIF-1α overexpression in oral squamous cell carcinoma: a meta-analysis" attempts to highlight hypoxia-inducible factor-1 alpha as a possible prognostic marker in oral squamous cell carcinoma (OSCC). We would like to underline a few points which may affect such a conclusion. The correlations between HIF-1α expression and tumour size as well as tumour stage are debatable. Further, the subgroup analysis incorporating Australia and Europe into a single subgroup limits the viability of the prognostic analysis of HIF-1α...
June 18, 2018: World Journal of Surgical Oncology
https://www.readbyqxmd.com/read/29911998/hif2%C3%AE-in-the-uterine-stroma-permits-embryo-invasion-and-luminal-epithelium-detachment
#10
Leona Matsumoto, Yasushi Hirota, Tomoko Saito-Fujita, Norihiko Takeda, Tomoki Tanaka, Takehiro Hiraoka, Shun Akaeda, Hidetoshi Fujita, Ryoko Shimizu-Hirota, Shota Igaue, Mitsunori Matsuo, Hirofumi Haraguchi, Mayuko Saito-Kanatani, Tomoyuki Fujii, Yutaka Osuga
Although it has been reported that hypoxia inducible factor 2 α (Hif2a), a major transcriptional factor inducible by low oxygen tension, is expressed in the mouse uterus during embryo implantation, its role in pregnancy outcomes remains unclear. This study aimed to clarify functions of uterine HIF using transgenic mouse models. Mice with deletion of Hif2a in the whole uterus (Hif2a-uKO mice) showed infertility due to implantation failure. Supplementation with progesterone (P4) and leukemia inhibitory factor (LIF) restored decidual growth arrest and aberrant position of implantation sites in Hif2a-uKO mice, respectively, but did not rescue pregnancy failure...
June 18, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29909605/anemia-in-conventional-hemodialysis-finding-the-optimal-treatment-balance
#11
Takeshi Hasegawa, Fumihiko Koiwa, Tadao Akizawa
Renal anemia is a serious and common complication in hemodialysis (HD) patients. The introduction of erythropoiesis-stimulating agents (ESAs) has dramatically improved hemoglobin levels and outcomes. Several interventional studies reported that excessive correction of anemia and the massive use of ESA can trigger cardiovascular disease (CVD), and consequently may worsen the prognosis of patients undergoing HD. Therefore, it has been widely recognized that large doses of ESA should be used with caution. An effective use of iron preparations is required to yield the optimal effect of ESA...
June 17, 2018: Seminars in Dialysis
https://www.readbyqxmd.com/read/29908837/expression-of-agpat2-an-enzyme-involved-in-the-glycerophospholipid-triacylglycerol-biosynthesis-pathway-is-directly-regulated-by-hif-1-and-promotes-survival-and-etoposide-resistance-of-cancer-cells-under-hypoxia
#12
Eleni-Anastasia Triantafyllou, Eleni Georgatsou, Ilias Mylonis, George Simos, Efrosyni Paraskeva
Hypoxia inducible factor-1 (HIF-1) supports survival of normal cells under low oxygen concentration and cancer cells in the hypoxic tumor microenvironment. This involves metabolic reprogramming via upregulation of glycolysis, downregulation of oxidative phosphorylation and, less well documented, effects on lipid metabolism. To investigate the latter, we examined expression of relevant enzymes in cancer cells grown under hypoxia. We show that expression of acylglycerol-3-phosphate acyltransferase 2 (AGPAT2), also known as lysophosphatidic acid acyltransferase β (LPAATβ), was upregulated under hypoxia and this was impaired by siRNA-mediated knockdown of HIF-1α...
June 14, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29908372/association-of-fibrotic-remodeling-and-cytokines-chemokines-content-in-epicardial-adipose-tissue-with-atrial-myocardial-fibrosis-in-patients-with-atrial-fibrillation
#13
Ichitaro Abe, Yasushi Teshima, Hidekazu Kondo, Haruka Kaku, Shintaro Kira, Yuki Ikebe, Shotaro Saito, Akira Fukui, Tetsuji Shinohara, Kunio Yufu, Mikiko Nakagawa, Naoki Hijiya, Masatsugu Moriyama, Tatsuo Shimada, Shinji Miyamoto, Naohiko Takahashi
BACKGROUND: Epicardial adipose tissue (EAT) is associated with atrial fibrillation (AF), but the underlying mechanisms remain to be fully elucidated. OBJECTIVE: Using human left atrial appendage (LAA) samples, we examined the interactive relationship between the EAT profile and atrial myocardial fibrosis through histological and biochemical analyses. METHODS: LAA samples were obtained from 59 consecutive AF patients during cardiovascular surgery...
June 13, 2018: Heart Rhythm: the Official Journal of the Heart Rhythm Society
https://www.readbyqxmd.com/read/29908122/sphingolipids-in-inflammatory-hypoxia
#14
Ulrike G Glaser, Joachim Fandrey
Hypoxia due to rapid tumor growth with impaired neovascularization and inflammation resulting from immune cell activation are hallmarks of cancer. Hypoxia-inducible factors (HIFs) control transcriptional adaptation in response to low oxygen conditions, both in tumor and immune cells. In addition, sphingolipids become increasingly recognized as important cell mediators in tumor and inflammatory hypoxia. Recent studies have identified acid sphingomyelinase (ASM), a central enzyme in the sphingolipid metabolism, as a regulator of several types of stress stimuli pathways and an important player in the tumor microenvironment...
June 1, 2018: Biological Chemistry
https://www.readbyqxmd.com/read/29907082/paravertebral-dexmedetomidine-as-an-adjuvant-to-ropivacaine-protects-against-independent-lung-injury-during-one-lung-ventilation-a-preliminary-randomized-clinical-trial
#15
Wei Zhang, Shanfeng Zhang, Bing Li, Mingyang Sun, Jiaqiang Zhang
BACKGROUND: To investigate the effect of paravertebral dexmedetomidine as an adjuvant to ropivacaine on independent lung injury during one-lung ventilation. METHODS: In total, 120 patients who underwent elective radical resection of pulmonary carcinoma were randomly assigned to one of six groups (n = 20): normal saline (C group), ropivacaine (R group), intravenous dexmedetomidine (Div group), 0.5 μg/kg paravertebral dexmedetomidine as an adjuvant to ropivacaine (RD0...
June 15, 2018: BMC Anesthesiology
https://www.readbyqxmd.com/read/29906224/high-salt-intake-shifts-the-mechanisms-of-flow-induced-dilation-in-the-middle-cerebral-arteries-of-sprague-dawley-rats
#16
Anita Matic, Ivana Jukic, Ana Stupin, Lidija Baric, Zrinka Mihaljevic, Sanela Unfirer, Ivana Tartaro Bujak, Branka Mihaljevic, Julian H Lombard, Ines Drenjancevic
The goal of this study was to examine the effect of 1-week of high salt (HS) intake and the role of oxidative stress in changing the mechanisms of flow-induced dilation (FID) in isolated pressurized middle cerebral arteries (MCA) of male Sprague-Dawley rats (N=15-16/per group). Reduced FID in the HS group was restored by intake of the superoxide scavenger TEMPOL (HS+TEMPOL in vivo group). Nitric oxide synthases (NOS) inhibitor Nω -nitro-L-arginine methyl ester (L-NAME), COX inhibitor indomethacin (INDO) and selective inhibitor of microsomal CYP450 epoxidase activity N-(methylsulfonyl)-2-(2-propynyloxy)-benzenehexanamide (MS-PPOH) significantly reduced FID in the LS group, while FID in the HS group was mediated by NO only...
June 15, 2018: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/29905853/2-methoxyestradiol-inhibits-hypoxia-induced-scleroderma-fibroblast-collagen-synthesis-by-phosphatidylinositol-3-kinase-akt-mtor-signalling
#17
Xing Zhou, Chaofan Liu, Jinghao Lu, Lubing Zhu, Ming Li
Objectives: To investigate the mechanism of 2-methoxyestradiol (2-ME) in inhibiting hypoxia-induced collagen synthesis of fibroblasts in SSc. Methods: The expressions of hypoxia-inducible factor 1 alpha (HIF-1α) and connective tissue growth factor (CTGF) in skin specimens derived from SSc patients and healthy volunteers were examined by immunohistochemistry. HIF-1α was knocked down by lentiviral transduction, and SSc dermal fibroblasts cultured under normoxic (21% O2) or hypoxic (1% O2) condition were treated with PI3K inhibitor LY294002, rapamycin or 2-ME (25 μM)...
June 13, 2018: Rheumatology
https://www.readbyqxmd.com/read/29905041/-comparative-study-on-biological-characteristics-between-different-generations-of-rabbit-nucleus-pulposus-cells
#18
Qi Chen, Fangfang Shi, Xi Yang, Limin Liu, Yueming Song
Objective: To research the biological characteristics of different generations of rabbit nucleus pulposus cells (NPCs) that were cultured with natural culture and subculture method. Methods: The thoracolumbar segments of New Zealand white rabbits (6-8 weeks old and weighing 1.5-2.5 kg) were obtained and nucleus pulposus were isolated from disc regions. And NPCs were harvested by enzymatic digestion from nucleus pulposus. Primary NPCs were counted as P0 generation...
June 1, 2018: Chinese Journal of Reparative and Reconstructive Surgery
https://www.readbyqxmd.com/read/29904944/hypoxia-inducible-factor-1%C3%AE-vascular-endothelial-growth-factor-signaling-activation-correlates-with-response-to-radiotherapy-and-its-inhibition-reduces-hypoxia-induced-angiogenesis-in-lung-cancer
#19
Hongjun Zhu, Shuanglin Zhang
Like other tumors, lung cancer must induce angiogenesis as it grows. Hypoxia-inducible factor 1α (HIF-1α) is the inducible subunit of the HIF-1 transcription factor that regulates genes involved in the response to hypoxia, some of which contributes to angiogenesis. Vascular endothelial growth factor (VEGF) is one of the genes upregulated by HIF-1 and is the primary cytokine in relation to angiogenesis. In this study we tested whether aberrant activation of hypoxia inducible factor-1α/vascular endothelial growth factor (HIF-1α/VEGF) pathway correlates with response to radiotherapy and examined the response of lung cancer cells to hypoxia in vitro...
June 15, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29904409/effects-of-hsya-on-the-proliferation-and-apoptosis-of-mscs-exposed-to-hypoxic-and-serum-deprivation-conditions
#20
Xiaoqing Song, Lining Su, Haifeng Yin, Jin Dai, Huiping Wei
As a primary active ingredient of safflor yellow, hydroxysafflor yellow A (HSYA) exhibits notable antioxidative and neuroprotective effects. The aim of the present study was to investigate the protective effects of HSYA in mesenchymal stem cells (MSCs) exposed to hypoxia (5% O2 ) and serum deprivation (H/SD), and to explore the mechanisms underlying HSYA-mediated protection. Under H/SD conditions, HSYA was applied to protect MSCs against injury. Cell viability, proliferation, apoptosis and reactive oxygen species (ROS) levels were determined using an 5-ethynyl-2'-deoxyuridine assay, MTT assay, Hoechst 33342/propidium iodide and 2',7'-dichlorodihydrofluorescein diacetate staining, respectively...
June 2018: Experimental and Therapeutic Medicine
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