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Hif 2

Sheng-Li Yang, Cui Zeng, Xiefan Fang, Qian-Jin He, Li-Ping Liu, Shi-Yun Bao, Xiaoli Pan, Zhi-Fan Xiong
Golgi Protein 73 (GP73) is a newly identified diagnostic and prognostic marker for liver cancer. GP73 is highly expressed in liver cancer tissues, however, the mechanism of its overexpression in tumors remains unknown. In the present study, the effect of hepatitis B virus (HBV) on GP73 expression was investigated in HepG2 cells, which are negative for HBV, and in HepG2.2.12 cells, which are integrated with HBV, using reverse transcription-quantitative polymerase chain reaction and western blot analysis. In addition, the cells were transfected with plasmid constructs overexpressing hepatitis B virus protein X (HBx), hypoxia-inducible factor (HIF)-1α, or HIF-2α in order to examine their roles in GP73 expression...
April 2018: Oncology Letters
Violaine Sironval, Laurence Reylandt, Perrine Chaurand, Saloua Ibouraadaten, Mihaly Palmai-Pallag, Yousof Yakoub, Bernard Ucakar, Jérôme Rose, Claude Poleunis, Rita Vanbever, Etienne Marbaix, Dominique Lison, Sybille van den Brule
Rechargeable Li-ion batteries (LIB) are increasingly produced and used worldwide. LIB electrodes are made of micrometric and low solubility particles, consisting of toxicologically relevant elements. The health hazard of these materials is not known. Here, we investigated the respiratory hazard of three leading LIB components (LiFePO4 or LFP, Li4 Ti5 O12 or LTO, and LiCoO2 or LCO) and their mechanisms of action. Particles were characterized physico-chemically and elemental bioaccessibility was documented. Lung inflammation and fibrotic responses, as well as particle persistence and ion bioavailability, were assessed in mice after aspiration of LIB particles (0...
March 17, 2018: Archives of Toxicology
Hung-Wei Kan, Jung-Hsien Hsieh, Hsiung-Fei Chien, Yea-Huey Lin, Ti-Yen Yeh, Chi-Chao Chao, Sung-Tsang Hsieh
To understand the pathology and molecular signatures of microangiopathy in diabetic neuropathy, we systemically and quantitatively examined the morphometry of microvascular and nerve pathologies of sural nerves. In the endoneurium of diabetic nerves, prominent microangiopathy evidenced by reduced capillary luminal area, increased capillary basement membrane thickness, and increased proportion of fibrin(+) blood vessels. Furthermore, capillary basement membrane thickness and the proportion of fibrin(+) blood vessels were correlated with small myelinated fiber density in diabetic nerves...
March 16, 2018: Disease Models & Mechanisms
Regina Trollmann, Theresa Mühlberger, Mandy Richter, Gudrun Boie, Andreas Feigenspan, Florian Brackmann, Susan Jung
Angiogenesis due to hypoxic-ischemic (HI) injury represents a crucial compensatory mechanism of the developing brain that is mainly regulated by hypoxia-inducible transcription factors (HIF). Pharmacological stimulation of HIF is suggested as a neuroprotective option, however, studies of its effects on vascular development are limited. We analyzed the influence of the prolyl-4-hydroxylase inhibitor (PHI), FG-4497, and erythropoietin (rhEPO) on post-hypoxic angiogenesis (angiogenic growth factors, vessel structures) in the developing mouse brain (P7) assessed after a regeneration period of 72 h...
March 13, 2018: Brain Research
Weiheng Wang, Yang Wang, Guoying Deng, Jun Ma, Xiaodong Huang, Jiangming Yu, Yanhai Xi, Xiaojian Ye
Objective: Special hypoxic and hypertonic microenvironment in intervertebral discs (IVDs) decreases the treatment effect of cell transplantation. We investigated the hypothesis that hypoxic preconditioning (HP) could improve the therapeutic effect of bone mesenchymal stem cells (BMSCs) to IVD degeneration. Methods: BMSCs from green fluorescent protein-transgenic rats were pretreated with cobalt chloride (CoCl2 , 100  μ M, 24 h) for hypoxic conditions in vitro ...
2018: Stem Cells International
Ying Pang, Garima Gupta, Chunzhang Yang, Herui Wang, Thanh-Truc Huynh, Ziedulla Abdullaev, Svetlana D Pack, Melanie J Percy, Terence R J Lappin, Zhengping Zhuang, Karel Pacak
BACKGROUND: The role of the hypoxia signaling pathway in the pathogenesis of pheochromocytoma/paraganglioma (PPGL)-polycythemia syndrome has been elucidated. Novel somatic mutations in hypoxia-inducible factor type 2A (HIF2A) and germline mutations in prolyl hydroxylase type 1 and type 2 (PHD1 and PHD2) have been identified to cause upregulation of the hypoxia signaling pathway and its target genes including erythropoietin (EPO) and its receptor (EPOR). However, in a minority of patients presenting with this syndrome, the genetics and molecular pathogenesis remain unexplained...
March 13, 2018: BMC Cancer
F Wu, S Wu, X Gou
Clear cell renal cell carcinoma (ccRCC) is the most common type of renal cancer in adults. The aim of this study is to identify the biomarkers and potential molecular mechanisms of ccRCC. Three gene expression profiles and two miRNA expression profiles were downloaded from GEO database. A total of 330 up-regulated differentially expressed genes (DEGs), 545 down-regulated DEGs, 26 up-regulated differentially expressed miRNAs (DEMs) and 11 down-regulated DEMs were identified by GEO2R. The gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed by KOBAS software...
2018: Neoplasma
Monica Currò, Tiziana Russo, Nadia Ferlazzo, Daniela Caccamo, Pietro Antonuccio, Salvatore Arena, Saveria Parisi, Patrizia Perrone, Riccardo Ientile, Carmelo Romeo, Pietro Impellizzeri
Balanitis xerotica obliterans (BXO) is a chronic inflammatory skin disorder, considered the male genital variant of lichen sclerosus. Anti-inflammatory drugs are commonly used in BXO. We evaluated the effects of an innovative formulation of ozonated olive oil with vitamin E acetate (OZOILE® ) on the inflammatory status and tissue remodeling in male children with BXO. The mRNA transcripts of proteins involved either in inflammation or in dynamics of tissue regeneration were analyzed by quantitative real-time PCR, in foreskins affected by BXO removed from patients untreated or treated with OZOILE® cream for 7 days before circumcision...
March 13, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Ji-Chang Wang, Xiong-Xiong Li, Xin Sun, Guang-Yue Li, Jing-Lan Sun, Yuan-Peng Ye, Long-Long Cong, Wei-Ming Li, Shao-Ying Lu, Jun Feng, Pei-Jun Liu
Substantial data from preclinical studies have revealed the biphasic effects of statins on cardiovascular angiogenesis. Although some have reported the anti-angiogenic potential of statins in malignant tumors, however, the underlying mechanism remains poorly understood. The aim of this study is to elucidate the mechanism by which simvastatin, a member of the statin family, inhibits tumor angiogenesis. Simvastatin significantly suppressed tumor cells-conditioned medium (TCM)-induced angiogenic promotion in vitro, and resulted in a dose-dependent anti-angiogenesis in vivo...
March 13, 2018: Cancer Science
Jeffrey D Bryant, Michael C Brown, Mikhail I Dobrikov, Elena Y Dobrikova, Sarah L Gemberling, Qing Zhang, Matthias Gromeier
Death associated protein 5 (DAP5) is an atypical isoform of the translation initiation scaffolds eukaryotic initiation factors 4GI and II (eIF4GI/II), which recruit mRNAs to ribosomes in mammals. Unlike eIF4GI/II, DAP5 binds eIF2β, a subunit of the eIF2 complex that delivers methionyl-tRNA to ribosomes. We discovered that DAP5:eIF2β binding depends on specific stimuli, e.g. protein kinase C (PKC)-Raf-ERK1/2 signals, and determines DAP5's influence on global and template-specific translation. DAP5 depletion caused an unanticipated surge of hypoxia-inducible factor 1α (HIF-1α), the transcription factor and master switch of the hypoxia response...
March 12, 2018: Molecular and Cellular Biology
Wei-Lun Tang, Wei-Hsin Tang, Andras Szeitz, Jayesh Kulkarni, Pieter Cullis, Shyh-Dar Li
The solvent-assisted active loading technology (SALT) was developed for encapsulating a water insoluble weak base into the liposomal core in the presence of 5% DMSO. In this study, we further examined the effect of various water miscible solvents in promoting active loading of other types of drugs into liposomes. To achieve complete drug loading, the amount of solvent required must result in complete drug solubilization and membrane permeability enhancement, but must be below the threshold that induces liposomal aggregation or causes bilayer disruption...
March 3, 2018: Biomaterials
Jinfeng Qu, Lei Zhang, Lanyu Li, Yujie Su
This study was aimed to investigate the tumor suppressive role of miR-148b in regulating endoplasmic reticulum metalloprotease 1 (ERMP1) expression and oxidative stress response in endometrial cancer cells. Human endometrial cancer RL95-2 cells were used and transfected with miR-148b mimic, miR-148b inhibitor, and their scrambled negative control. Thereafter, the transfection efficiency was determined by qRT-PCR and cell viability was assessed by MTT assay. The luciferase reporter assay, Western blot, and qRT-PCR were conducted to determine the target gene of miR-148b...
March 9, 2018: Oncology Research
Martine I Abboud, Tom E McAllister, Ivanhoe K H Leung, Rasheduzzaman Chowdhury, Christian Jorgensen, Carmen Domene, Jasmin Mecinović, Kerstin Lippl, Rebecca L Hancock, Richard J Hopkinson, Akane Kawamura, Timothy D W Claridge, Christopher J Schofield
Prolyl hydroxylation of hypoxia inducible factor (HIF)-α, as catalysed by the Fe(ii)/2-oxoglutarate (2OG)-dependent prolyl hydroxylase domain (PHD) enzymes, has a hypoxia sensing role in animals. We report that binding of prolyl-hydroxylated HIF-α to PHD2 is ∼50 fold hindered by prior 2OG binding; thus, when 2OG is limiting, HIF-α degradation might be inhibited by PHD binding.
March 9, 2018: Chemical Communications: Chem Comm
Hitoshi Itoh, Tsuyoshi Kadomatsu, Hironori Tanoue, Masaki Yugami, Keishi Miyata, Motoyoshi Endo, Jun Morinaga, Eisuke Kobayashi, Takeshi Miyamoto, Ryoma Kurahashi, Kazutoyo Terada, Hiroshi Mizuta, Yuichi Oike
The tumor microenvironment promotes epigenetic changes in tumor cells associated with tumor aggressiveness. Here we report that in primary tumor cells, increased interleukin-6 (IL-6) expression brought on by DNA demethylation of its promoter by ten-eleven translocation 2 (TET2) promotes lung metastasis in osteosarcoma (OS). Xenograft experiments show increased IL-6 expression and decreased methylation of its promoter in OS cells after implantation relative to before implantation. In addition, changes in IL-6 methylation and expression seen in OS cells at the primary site were maintained at the metastatic site...
March 8, 2018: Oncogene
Ru Zhao Dong, Feng Xiao Dong, Qi Tianq Liu, Ting Xu Zhi, Jie Zou, Tao Jing Zhong, Tao Li, Lan Xiang Mo, Wei Zhou, Wen Wen Guo, Xia Liu, Yuan Yuan Chen, Yang Meng Li, Xiao Gang Zhong, Min Ya Han, Hao Zhong Wang
PURPOSE: Hypoxia-inducible factor (HIF)-2α is regarded as a preferential target for individualized HCC treatment and sorafenib resistance. Our study aimed to identify the regulatory mechanisms of HIF-2α activity under hypoxic conditions. We sought to determine whether the COX-2/PGE2 axis is involved in the regulatory mechanisms of HIF-2α activity and of sorafenib resistance in hypoxic HCC cells. EXPERIMENTAL DESIGN: The cell viability, migration and invasion abilities were measured to analyze the effects of HIF-2α on hypoxic HCC cells...
March 7, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Gang Xu
Activation of the transcription factor hypoxia inducible factor‑1α (HIF-1α) is considered critical for the stimulation of osteogenic markers including runt‑related transcription factor 2 (Runx2), alkaline phosphatase (ALP) and osteocalcin, which are closely associated with forkhead boxclass O1 (Foxo1) levels in osteoblasts. The present study explored the associations between HIF‑1α and Foxo1 in the regulation of cell viability, proliferation and apoptosis of osteoblasts. Osteoblasts obtained from children's iliac cancellous bone were used in the present study, which were confirmed by immunofluorescence staining for the osteoblast marker osteocalcin...
March 5, 2018: Molecular Medicine Reports
Theodoros Eleftheriadis, Georgios Pissas, Vassilios Liakopoulos, Ioannis Stefanidis
Indoleamine 2, 3-dioxygenase (IDO) suppresses T-cell function at least in part by altering cell metabolism. Hypoxia-inducible factor-1 (HIF-1) increases upon T-cell activation and alters cell metabolism favoring their differentiation to effector cells. The effect of IDO on HIF-1α expression and activity was evaluated. For this purpose, mixed lymphocyte reaction (MLR) was performed using the IDO inhibitor 1-DL-methyl-tryptophan and the p53 inhibitor pifithrin-α. L-tryptophan degradation and cell proliferation were assessed by enzyme-linked immunosorbent assay, whereas the expression of proteins of interest by western blotting...
February 2018: Iranian Journal of Allergy, Asthma, and Immunology
Fei Hong, Lu Wan, Jie Liu, Ke Huang, Zhenmeng Xiao, Yingjing Zhang, Chunwei Shi
Liver fibrosis is characterized by deposition of excessive extracellular matrix (ECM). The major source of ECM is activated hepatic stellate cells (HSCs). Previously, we reported that hypoxia-inducible factor-1 (Hif-1) regulates activation of HSCs through autophagy. In current work, human HSC cell line LX-2 was used as cell model. It was determined that trimethylation of H3 histone on lysine 4 (H3K4me3) occurred in the Hif-1 transcriptional complex. Inhibition of modifications of histone methylation suppressed Hif-1 nuclear transport, autophagosome formation, and activation of LX-2 cells...
March 2018: FEBS Open Bio
Alexey Surov, Hans Jonas Meyer, Andreas Wienke
OBJECT: Our purpose was to provide data regarding relationships between different imaging and histopathological parameters in HNSCC. METHODS: MEDLINE library was screened for associations between different imaging parameters and histopathological features in HNSCC up to December 2017. Only papers containing correlation coefficients between different imaging parameters and histopathological findings were acquired for the analysis. RESULTS: Associations between18 F-FDG positron emission tomography (PET) and KI 67 were reported in 8 studies (236 patients)...
March 3, 2018: Translational Oncology
Eduardo H Gilglioni, Jung-Chin Chang, Suzanne Duijst, Simei Go, Aziza A A Adam, Ruurdtje Hoekstra, Arthur J Verhoeven, Emy L Ishii-Iwamoto, Ronald P J Oude Elferink
Primary hepatocyte culture is an important in vitro system for the study of liver functions. In vivo , hepatocytes have high oxidative metabolism. However, oxygen supply by means of diffusion in in vitro static cultures is much less than that by blood circulation in vivo . Therefore, we investigated whether hypoxia contributes to dedifferentiation and deregulated metabolism in cultured hepatocytes. To this end, murine hepatocytes were cultured under static or shaken (60 revolutions per minute) conditions in a collagen sandwich...
March 2018: Hepatology Communications
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