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Hypoxia-inducible factor

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https://www.readbyqxmd.com/read/30110566/absence-of-renal-hypoxia-in-the-subacute-phase-of-severe-renal-ischemia-reperfusion-injury
#1
Connie P C Ow, Jennifer P Ngo, Md Mahbub Ullah, Giannie Barsha, Ruth C R Meex, Matthew J Watt, Lucinda M Hilliard, Maarten P Koeners, Roger G Evans
Tissue hypoxia has been proposed as an important event in renal ischemia reperfusion injury (IRI) particularly during the period of ischemia and in the immediate hours following reperfusion. However, little is known about renal oxygenation during the subacute phase of IRI. We employed four different methods to assess the temporal and spatial changes in tissue oxygenation during the subacute phase (24 h and 5 days after reperfusion) of a severe form of renal IRI in rats. We hypothesized that the kidney is hypoxic 24 h and 5 days after an hour of bilateral renal ischemia, driven by a disturbed balance between renal oxygen delivery (DO2) and oxygen consumption (VO2)...
August 15, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/30110121/neprilysin-inhibitors-as-a-new-approach-in-the-treatment-of-right-heart-failure-in-the-course-of-chronic-obstructive-pulmonary-disease
#2
Maciej Liczek, Iga Panek, Piotr Damiański, Olga Jęczeń, Jędrzej Jaźwiec, Piotr Kuna, Michał Panek
The aim of the study was to find out scientific evidence on the possible use of the combined angiotensin II receptor antagonist and neprilysin inhibitors (ARNI) in patients with right heart failure (RHF) in the course of chronic obstructive pulmonary disease (COPD). It has been proven that a lack of neprilysin or its reduced expression in hypoxia leads to exacerbation of pulmonary arterial remodelling (PAR) or pulmonary hypertension (PH) in the mechanism related to the platelet-derived growth factor (PDGF) resulting in the proliferation and migration of pulmonary artery smooth muscle cells and endothelial-to-mesenchymal transition...
August 15, 2018: Advances in Respiratory Medicine
https://www.readbyqxmd.com/read/30109021/recent-advances-in-the-management-of-malignant-pheochromocytoma-and-paraganglioma-focus-on-tyrosine-kinase-and-hypoxia-inducible-factor-inhibitors
#3
REVIEW
Rodrigo Toledo, Camilo Jimenez
Inactivating mutations of the succinate dehydrogenase subunit B ( SDHB ) gene and the subsequent stabilization and activation of the hypoxia-inducible factor 2-alpha (HIF2α) unit are recognized hallmarks associated with the development of metastatic pheochromocytomas and paragangliomas (MPPG). Despite this discovery, the development of systemic therapies for patients with MPPG has been very slow. The rarity of the disease, the lack of preclinical animal models, and the impracticable development of large clinical trials has hindered the therapeutic progress for MPPG...
2018: F1000Research
https://www.readbyqxmd.com/read/30108299/role-of-the-macrophage-migration-inhibitory-factor-mif-in-the-survival-of-first-trimester-human-placenta-under-induced-stress-conditions
#4
Francesca Ietta, Eloisa Amália Vieira Ferro, Estela Bevilacqua, Linda Benincasa, Emanuela Maioli, Luana Paulesu
Macrophage Migration Inhibitory Factor (MIF) is a multifunctional molecule highly secreted by human placenta mainly in the early phases of pregnancy. Studies in different cells show that MIF is a pro-survival factor by binding to its receptor CD74. By using the in vitro model of placental explants from first trimester pregnancy, we investigated the role of MIF in the survival of placental cells under induced stress conditions that promote apoptosis or mimic the hypoxia/re-oxygenation (H/R) injury that placenta could suffer in vivo...
August 14, 2018: Scientific Reports
https://www.readbyqxmd.com/read/30107337/angiopep-2-modified-pegylated-2-methoxyestradiol-micelles-to-treat-the-pc12-cells-with-oxygen-glucose-deprivation-reoxygenation
#5
Lijun Hu, Yun Wang, Yihui Zhang, Ning Yang, Huijie Han, Yuanyuan Shen, Derong Cui, Shengrong Guo
2-Methoxyestradiol (2ME2), as a microtubule and hypoxia-inducible factor-1 (HIF-1) inhibitor, can be used to treat cerebral ischemia-reperfusion (I/R) injury. However, its poor water solubility compromises its efficacy as a neuroprotectant. Herein, we synthesized PEGylated 2ME2 and angiopep-2 capped PEGylated 2ME2 and fabricated angiopep-2 modified PEGylated 2ME2 micelles containing free 2ME2 (ANG-PEG-2ME2/2ME2) via emulsion-solvent evaporation method. The effect of the micelles on ischemia-reoxygenation injury was evaluated by oxygen-glucose deprivation/reoxygenation (OGD/R) models with different degrees of PC12 cell damage...
August 8, 2018: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/30107094/preclinical-evidence-of-the-enhanced-effectiveness-of-combined-rapamycin-and-aicar-in-reducing-kidney-cancer
#6
Sitai Liang, Edward A Medina, Boajie Li, Samy L Habib
Loss of Von Hippel-Lindau (VHL) in renal carcinoma cells results in up regulation of the activity of Hypoxia-Inducible Factor (HIF-α), a major transcription factor involved in kidney cancer. Rapamycin as mTOR inhibitor and 5-aminoimidazole-4-carboxamide (AICA)-riboside (AICAR) as AMPK activator are separately used to treat cancer patients. In the current study, the possible additive effect of drug combinations in reducing kidney tumorigenesis was investigated. Treatment with drug combinations significantly decreased cell proliferation, increased cell apoptosis, and abolished Akt phosphorylation and HIF-2α expression in RCC cells, including primary cells isolated from kidney cancer patients...
August 14, 2018: Molecular Oncology
https://www.readbyqxmd.com/read/30106153/correlation-between-dec1-dec2-and-epithelial%C3%A2-mesenchymal-transition-in-human-prostate-cancer-pc%C3%A2-3-cells
#7
Qiang Liu, Yunyan Wu, Hiroko Seino, Toshihiro Haga, Tadashi Yoshizawa, Satoko Morohashi, Hiroshi Kijima
Differentiated embryonic chondrocyte (DEC) genes have been reported to be involved in the regulation of mammalian circadian rhythms, differentiation, apoptosis, the response to hypoxia and epithelial‑mesenchymal transition (EMT). Activation of transforming growth factor (TGF)‑β signaling is known to promote EMT for the development of metastatic castration‑resistant prostate cancer (PCa). However, the role of DEC genes in the TGF‑β‑induced EMT of PCa remains unclear. In the present study it was demonstrated that TGF‑β increased the transcriptional/translational levels of DEC1 but decreased those of DEC2 in PC‑3 cells...
August 9, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/30106145/pi3k-akt-and-hif%C3%A2-1-signaling-pathway-in-hypoxia%C3%A2-ischemia-review
#8
Zhen Zhang, Li Yao, Jinhua Yang, Zhenkang Wang, Gang Du
Hypoxia‑ischemia (H‑I) is frequently observed in perinatal asphyxia and other diseases. It can lead to serious cardiac injury, cerebral damage, neurological disability and mortality. Previous studies have demonstrated that the phosphatidylinositol‑3 kinase (PI3K)/protein kinase B (Akt) signaling pathway, which regulates a wide range of cellular functions, is involved in the resistance response to H‑I through the activation of proteins associated with survival and inactivation of apoptosis‑associated proteins...
August 9, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/30106084/hypoxic-preconditioned-bone-mesenchymal-stem-cells-ameliorate-spinal-cord-injury-in-rats-via-improved-survival-and-migration
#9
Weiheng Wang, Xiaodong Huang, Wenbo Lin, Yuanyuan Qiu, Yunfei He, Jiangming Yu, Yanhai Xi, Xiaojian Ye
The unique hypoxic inflammatory microenvironment observed in the spinal cord following spinal cord injury (SCI) limits the survival and efficacy of transplanted bone mesenchymal stem cells (BMSCs). The aim of the present study was to determine whether hypoxic preconditioning (HP) increased the therapeutic effects of BMSC on SCI. BMSCs were pretreated with cobalt chloride (CoCl2) in vitro, and the proliferative apoptotic and migratory abilities of these hypoxic BMSCs (H‑BMSCs) were assessed. BMSCs and H‑BMSCs derived from green fluorescent protein (GFP) rats were transplanted into SCI rats in vivo...
August 7, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/30105447/cell-specific-gene-therapy-driven-by-an-optimized-hypoxia-regulated-vector-reduces-choroidal-neovascularization
#10
Manas R Biswal, Howard M Prentice, George W Smith, Ping Zhu, Yao Tong, C Kathleen Dorey, Alfred S Lewin, Janet C Blanks
Aberrant growth of blood vessels in the choroid layer of the eye, termed choroidal neovascularization (CNV), is the pathological hallmark of exudative age-related macular degeneration (AMD), causing irreversible blindness among the elderly. Co-localization of proangiogenic factors and hypoxia inducible factors (HIF) in neovascular membranes from AMD eyes suggests the role of hypoxia in pathogenesis of CNV. In order to utilize hypoxic conditions in RPE for therapeutic purposes, we developed an optimized hypoxia regulated, RPE cell-specific gene therapy to inhibit choroidal neovascularization...
August 13, 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/30105440/hypoxia-induced-plod2-is-a-key-regulator-in-epithelial-mesenchymal-transition-and-chemoresistance-in-biliary-tract-cancer
#11
Yuichiro Okumura, Takehiro Noda, Hidetoshi Eguchi, Takuya Sakamoto, Yoshifumi Iwagami, Daisaku Yamada, Tadafumi Asaoka, Hiroshi Wada, Koichi Kawamoto, Kunihito Gotoh, Shogo Kobayashi, Yutaka Takeda, Masahiro Tanemura, Koji Umeshita, Yuichiro Doki, Masaki Mori
BACKGROUND: The prognosis of biliary tract cancer (BTC) is unfavorable due to its chemoresistance. Hypoxia triggers epithelial-to-mesenchymal transition (EMT), which is closely related to drug resistance. In this study, we focused on the functional roles of procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2), a hypoxia-induced gene, in BTC, and assessed the clinical significance of PLOD2. METHODS: The expression of PLOD2 under hypoxia was assessed in BTC cell lines...
August 13, 2018: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/30105105/bilateral-pheochromocytomas-in-a-patient-with-y175c-von-hippel-lindau-mutation
#12
Olga Astapova, Anindita Biswas, Alessandra DiMauro, Jacob Moalem, Stephen R Hammes
Von Hippel-Lindau (VHL) disease, caused by germline mutations in the VHL gene, is characterized by metachronously occurring tumors including pheochromocytoma, renal cell carcinoma (RCC), and hemangioblastoma. Although VHL disease leads to reduced life expectancy, its diagnosis is often missed and tumor screening guidelines are sparse. VHL protein acts as a tumor suppressor by targeting hypoxia-inducible factors (HIFs) for degradation through an oxygen-dependent mechanism. VHL mutants with more severely reduced HIF degrading function carry a high risk of RCC, while mutants with preserved HIF degrading capacity do not cause RCC but still lead to other tumors...
2018: Case Reports in Endocrinology
https://www.readbyqxmd.com/read/30104982/effects-of-hypoxia-and-bed-rest-on-markers-of-cardiometabolic-risk-compensatory-changes-in-circulating-trail-and-glutathione-redox-capacity
#13
Gianni Biolo, Filippo G Di Girolamo, Adam McDonnell, Nicola Fiotti, Filippo Mearelli, Roberta Situlin, Arianna Gonelli, Barbara Dapas, Mauro Giordano, Mitja Lainscak, Gabriele Grassi, Giorgio Zauli, Paola Secchiero, Igor Mekjavic
In chronic diseases, hypoxia and physical inactivity are associated with atherosclerosis progression. In contrast, a lower mortality from coronary artery disease and stroke is observed in healthy humans residing at high altitude in hypoxic environments. Eleven young, male volunteers completed the following 10-day campaigns in a randomized order: hypoxic ambulatory, hypoxic bed rest and normoxic bed rest. Before intervention, subjects were evaluated in normoxic ambulatory condition. Normobaric hypoxia was achieved in a hypoxic facility simulating 4000 m of altitude...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/30103950/inhibition-of-traf6-alleviates-choroidal-neovascularization-in-vivo
#14
Dongmei Ding, Manhui Zhu, Xiaojuan Liu, Li Jiang, Jiaowen Xu, Lili Chen, Juan Liang, Lele Li, Taohu Zhou, Ying Wang, Hao Shi, You Yuan, E Song
Choroidal neovascularization (CNV) is a type of wet age-related macular degeneration (AMD) which is a major cause of blindness in elder patients. Tumor necrosis factor receptor-associated factor 6 (TRAF6) promotes tumor angiogenesis via upregulating the expression of hypoxia-inducible factor 1α (HIF-1α) and vascular endothelial growth factor (VEGF). Additionally, TRAF6 facilitates the inflammatory response in macrophages and microglia. Here, using mouse laser-induced CNV model and TRAF6 siRNA, the study shows that TRAF6 is a critical player in CNV...
August 6, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/30103670/autosomal-dominant-retinitis-pigmentosa-associated-gene-prpf8-is-essential-for-hypoxia-induced-mitophagy-through-regulating-ulk1-mrna-splicing
#15
Guang Xu, Ting Li, Jiayi Chen, Changyan Li, Haixin Zhao, Chengcheng Yao, Hua Dong, Kaiqing Wen, Kai Wang, Jie Zhao, Qing Xia, Tao Zhou, Huafeng Zhang, Ping Gao, Ailing Li, Xin Pan
Aged and damaged mitochondria can be selectively degraded by specific autophagic elimination, termed mitophagy. Defects in mitophagy have been increasingly linked to several diseases including neurodegenerative diseases, metabolic diseases and other aging-related diseases. However, the molecular mechanisms of mitophagy are not fully understood. Here, we identify PRPF8 (pre-mRNA processing factor 8), a core component of the spliceosome, as an essential mediator in hypoxia-induced mitophagy from an RNAi screen based on a fluorescent mitophagy reporter, mt-Keima...
August 13, 2018: Autophagy
https://www.readbyqxmd.com/read/30103001/fraxinellone-has-anticancer-activity-in-vivo-by-inhibiting-programmed-cell-death-ligand-1-expression-by-reducing-hypoxia-inducible-factor-1%C3%AE-and-stat3
#16
Yue Xing, Chunliu Mi, Zhe Wang, Zhi Hong Zhang, Ming Yue Li, Hong Xiang Zuo, Jing Ying Wang, Xuejun Jin, Juan Ma
Dictamnus dasycarpus is a traditional Chinese medicine that has been commonly used in the treatment of cancer. Fraxinellone is a natural product isolated from the D. dasycarpus plant, which has been shown to exhibit neuroprotective and anti-inflammatory activities. However, whether fraxinellone exerts anticancer effects and the mechanisms by which it may inhibit tumor growth remain unknown. Here, we found that fraxinellone, in a dose-dependented manner, inhibited the expression of programmed cell death ligand-1 (PD-L1), which plays a pivotal role in tumorigenesis...
August 10, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/30102772/macrophage-specific-hif-1%C3%AE-contributes-to-impaired-autophagic-flux-in-non-alcoholic-steatohepatitis
#17
Xiaojing Wang, Marcelle Ribeiro, Arvin Iracheta-Vellve, Patrick Lowe, Aditya Ambade, Abhishek Satishchandran, Terence Bukong, Donna Catalano, Karen Kodys, Gyongyi Szabo
Inflammatory cell activation drives diverse cellular programming during hepatic diseases. Hypoxia-inducible factors (HIFs) have recently been identified as important regulators of immunity and inflammation. In non-alcoholic steatohepatitis (NASH), HIF-1α is upregulated in hepatocytes where it induces steatosis; however, the role of HIF-1α in macrophages under metabolic stress has not been explored. In this study, we found increased HIF-1α levels in hepatic macrophages in methionine-choline-deficient (MCD) diet-fed mice and in macrophages of NASH patients compared to controls...
August 13, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/30102510/tumor-oxygenation-and-hypoxia-inducible-factor-1-functional-inhibition-via-a-reactive-oxygen-species-responsive-nanoplatform-for-enhancing-radiation-therapy-and-abscopal-effects
#18
Lingtong Meng, Yali Cheng, Xiaoning Tong, Shaoju Gan, Yawen Ding, Yu Zhang, Chao Wang, Lei Xu, Yishen Zhu, Jinhui Wu, Yiqiao Hu, Ahu Yuan
Hypoxia, and hypoxia-inducible factor-1 (HIF-1), can induce tumor resistance to radiation therapy. To overcome hypoxia-induced radiation resistance, recent studies have described nano-systems to improve tumor oxygenation for immobilizing DNA damage and simultaneously initiate oxygen-dependent HIF-1α degradation. However, HIF-1α degradation is incomplete during tumor oxygenation treatment alone. Therefore, tumor oxygenation combined with residual HIF-1 functional inhibition is crucial to optimizing therapeutic outcomes of radiotherapy...
August 13, 2018: ACS Nano
https://www.readbyqxmd.com/read/30100905/glycogen-metabolism-and-rheumatoid-arthritis-the-role-of-glycogen-synthase-1-in-regulation-of-synovial-inflammation-via-blocking-amp-activated-protein-kinase-activation
#19
Maohua Shi, Jingnan Wang, Youjun Xiao, Cuicui Wang, Qian Qiu, Minxi Lao, Yangtao Yu, Zhifeng Li, Hongwei Zhang, Yujin Ye, Liuqin Liang, Xiuyan Yang, Guoqiang Chen, Hanshi Xu
Objective: To investigate the role of glycogen metabolism in regulating rheumatoid fibroblast-like synoviocyte (FLS)-mediated synovial inflammation and its underlying mechanism. Methods: FLSs were separated from synovial tissues (STs) obtained from rheumatoid arthritis (RA) patients. Glycogen content was determined by periodic acid Schiff staining. Protein expression was analyzed by Western blot or immunohistochemistry. Gene expression of cytokines and matrix metalloproteinases (MMPs) was evaluated by quantitative real-time PCR...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/30100770/swimming-induced-pulmonary-edema-current-perspectives
#20
REVIEW
Ralph Smith, Julian O M Ormerod, Nikant Sabharwal, Courtney Kipps
With the growing popularity of water-based sports, cases of swimming-induced pulmonary edema (SIPE) are becoming increasingly recognized. SIPE, a potentially life-threatening condition, is an acute cause of breathlessness in athletes. It has been described frequently in scuba divers, swimmers, and triathletes and is characterized by symptoms and signs of pulmonary edema following water immersion. It is important to recognize that athletes' symptoms can present with a spectrum of severity from mild breathlessness to severe dyspnea, hemoptysis, and hypoxia...
2018: Open Access Journal of Sports Medicine
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