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https://www.readbyqxmd.com/read/29792309/metabolic-and-physiologic-imaging-biomarkers-of-the-tumor-microenvironment-predict-treatment-outcome-with-radiation-or-a-hypoxia-activated-prodrug-in-mice
#1
Shingo Matsumoto, Shun Kishimoto, Keita Saito, Yoichi Takakusagi, Jeeva P Munasinghe, Nallathamby Devasahayam, Charles Hart, Robert J Gillies, James B Mitchell, Murali C Krishna
Pancreatic ductal adenocarcinoma (PDAC) is characterized by hypoxic niches that lead to treatment resistance. Therefore, studies of tumor oxygenation and metabolic profiling should contribute to improved treatment strategies. Here we define two imaging biomarkers that predict differences in tumor response to therapy: 1) partial oxygen pressure (pO2), measured by EPR imaging; and 2) [1-13C] pyruvate metabolism rate, measured by hyperpolarized 13C MRI. Three human PDAC xenografts with varying treatment sensitivity (Hs766t, MiaPaCa-2, and Su...
May 23, 2018: Cancer Research
https://www.readbyqxmd.com/read/29791970/effect-of-high-intensity-resistance-circuit-based-training-in-hypoxia-on-aerobic-performance-and-repeat-sprint-ability
#2
Domingo J Ramos-Campo, Ismael Martínez-Guardado, Guillermo Olcina, Cristian Marín-Pagán, Francisco J Martínez-Noguera, Jorge Carlos-Vivas, Pedro E Alcaraz, Jacobo A Rubio-Arias
Recent acute studies have shown that high-intensity resistance circuit-based (HRC) training in hypoxia increases metabolic stress. However, no intervention studies have yet proven their effectiveness. This study aimed to analyse the effect of 8 weeks of HRC in hypoxia on aerobic performance, resting energy expenditure (REE), repeat sprint ability (RSA) and haematological variables. Twenty-eight subjects were assigned to hypoxia (FiO2 =15%; HRChyp : n=15; age: 24.6±6.8 years; height: 177.4±5.9 cm; weight: 74...
May 23, 2018: Scandinavian Journal of Medicine & Science in Sports
https://www.readbyqxmd.com/read/29791781/a-dual-role-of-mir-22-in-rhabdomyolysis-induced-acute-kidney-injury-aki
#3
Susanne Mathia, Lucas J Rudigier, Mumtaz Kasim, Karin M Kirschner, Pontus B Persson, Kai-Uwe Eckardt, Christian Rosenberger, Michael Fähling
AIM: In acute kidney injury (AKI) regions of the kidney are hypoxic. However, for reasons yet unknown, adaptation to hypoxia through hypoxia inducible factor (HIF) is limited. Here we studied miR-22, a potential HIF repressor, in normal kidneys, as well as in rhabdomyolysis-induced AKI, a condition where miR-22 is up-regulated. METHODS: AKI in mice was provoked by IM injection of glycerol. Tissue homogenates were processed to determine the levels of candidate RNAs and proteins, as well as global gene expression profiles...
May 23, 2018: Acta Physiologica
https://www.readbyqxmd.com/read/29791586/hypoxia-induced-hyperpermeability-of-rat-glomerular-endothelial-cells-involves-hif-2%C3%AE-mediated-changes-in-the-expression-of-occludin-and-zo-1
#4
Peng-Li Luo, Yan-Jun Wang, Yan-Yan Yang, Jia-Jia Yang
This study aimed to investigate the role of hypoxia-inducible factor-2α (HIF-2α) in the expression of tight junction proteins and permeability alterations in rat glomerular endothelial cells (rGENCs) under hypoxia conditions. The expression level of HIF-2α and tight junction proteins (occludin and ZO-1) in rGENCs were examined following 5% oxygen density exposure at different treatment times. HIF-2α lentivirus transfection was used to knockdown HIF-2α expression. Cells were divided into four groups: 1) control group (rGENCs were cultured under normal oxygen conditions), 2) hypoxia group (rGENCs were cultured under hypoxic conditions), 3) negative control group (rGENCs were infected with HIF-2α lentivirus negative control vectors and cultured under hypoxic conditions), and 4) Len group (rGENCs were transfected with HIF-2α lentivirus and cultured under hypoxic conditions)...
2018: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://www.readbyqxmd.com/read/29791568/assessing-the-association-between-hypoxia-during-craniofacial-development-and-oral-clefts
#5
Erika Calvano Küchler, Lea Assed da Silva, Paulo Nelson-Filho, Ticiana M Sabóia, Angela M Rentschler, José Mauro Granjeiro, Driely Oliveira, Patricia N Tannure, Raquel Assed da Silva, Leonardo Santos Antunes, Michael Tsang, Alexandre R Vieira
Objectives To evaluate the association between hypoxia during embryo development and oral clefts in an animal model, and to evaluate the association between polymorphisms in the HIF-1A gene with oral clefts in human families. Material and Methods The study with the animal model used zebrafish embryos at 8 hours post-fertilization submitted to 30% and 50% hypoxia for 24 hours. At 5 days post-fertilization, the larvae were fixed. The cartilage structures were stained to evaluate craniofacial phenotypes. The family-based association study included 148 Brazilian nuclear families with oral clefts...
2018: Journal of Applied Oral Science: Revista FOB
https://www.readbyqxmd.com/read/29790920/elucidating-the-role-of-the-maternal-embryonic-leucine-zipper-kinase-melk-in-adrenocortical-carcinoma
#6
Katja Kiseljak-Vassiliades, Yu Zhang, Adwitiya Kar, Raud Razzaghi, Mei Xu, Katherine Gowan, Christopher D Raeburn, Maria Albuja-Cruz, Kenneth L Jones, Hilary Somerset, Lauren Fishbein, Stephen Leong, Margaret E Wierman
Adrenocortical carcinoma (ACC) is an aggressive cancer with a five-year survival less than 35%. Mortality remains high due to lack of targeted therapies. Using bioinformatic analyses, we identified Maternal Embryonic Leucine Zipper Kinase (MELK) as 4.1-fold overexpressed in ACC compared to normal adrenal samples. High MELK expression in human tumors correlated with shorter survival and with increased expression of genes involved in cell division and growth. We investigated the functional effects of MELK inhibition using newly developed ACC cell lines with variable MELK expression, CU-ACC1 and CU-ACC2, compared with H295R cells...
May 21, 2018: Endocrinology
https://www.readbyqxmd.com/read/29790425/hypoxic-preconditioning-reduces-propofol-induced-neuroapoptosis-via-regulation-of-bcl-2-and-bax-and-downregulation-of-activated-caspase-3-in-the-hippocampus-of-neonatal-rats
#7
Jing Lv, Yubing Liang, Youbing Tu, Jing Chen, Yubo Xie
OBJECTIVE:  Evidence has shown that propofol may cause widespread apoptotic neurodegeneration. Hypoxic preconditioning (HPC) was previously demonstrated to provide neuroprotection and brain recovery from either acute or chronic neurodegeneration in several cellular and animal models. Therefore, the present study was designed to investigate the protective effects of hypoxic preconditioning on apoptosis caused by propofol in neonatal rats. METHODS: Propofol (100 mg/kg) was given to 7-day-old (P7) Sprague Dawley pups...
May 23, 2018: Neurological Research
https://www.readbyqxmd.com/read/29790026/pathogenetic-role-of-the-stress-induced-release-of-glucocorticoid-hormones-in-the-development-of-post-traumatic-stress-disorder-an-experimental-study
#8
M Y Zenko, K A Baranova, E A Rybnikova
In the rat experimental model of posttraumatic stress disorder (PTSD), the level of blood corticosterone was at least eight-fold increased (an overrelease). The use of hypobaric hypoxic preconditioning or short-term inhibition of glucocorticoid synthesis by metyrapone injection prevented development of the experimental PTSD.
March 2018: Doklady Biological Sciences: Proceedings of the Academy of Sciences of the USSR, Biological Sciences Sections
https://www.readbyqxmd.com/read/29789585/hypoxia-induces-senescence-of-bone-marrow-mesenchymal-stem-cells-via-altered-gut-microbiota
#9
Junyue Xing, Yongquan Ying, Chenxi Mao, Yiwei Liu, Tingting Wang, Qian Zhao, Xiaoling Zhang, Fuxia Yan, Hao Zhang
Systemic chronic hypoxia is a feature of many diseases and may influence the communication between bone marrow (BM) and gut microbiota. Here we analyse patients with cyanotic congenital heart disease (CCHD) who are experiencing chronic hypoxia and characterize the association between bone marrow mesenchymal stem cells (BMSCs) and gut microbiome under systemic hypoxia. We observe premature senescence of BMSCs and abnormal D-galactose accumulation in patients with CCHD. The hypoxia that these patients experience results in an altered diversity of gut microbial communities, with a remarkable decrease in the number of Lactobacilli and a noticeable reduction in the amount of enzyme-degraded D-galactose...
May 22, 2018: Nature Communications
https://www.readbyqxmd.com/read/29789575/tamoxifen-induced-knockdown-of-the-mitochondrial-calcium-uniporter-in-thy1-expressing-neurons-protects-mice-from-hypoxic-ischemic-brain-injury
#10
Matthew Nichols, Evgeny V Pavlov, George S Robertson
The mitochondrial calcium uniporter (MCU) mediates high-capacity mitochondrial calcium uptake that stimulates energy production. However, excessive MCU activity can cause ischemic heart injury. To examine if the MCU is also involved in hypoxic/ischemic (HI) brain injury, we have generated conditional MCU knockout mice by tamoxifen (TMX) administration to adult MCU-floxed (MCUfl/fl ) mice expressing a construct encoding Thy1-cre/ERT2-eYFP. Relative to TMX/Thy1-cre/ERT2-eYFP controls, HI-induced sensorimotor deficits, forebrain neuron loss and mitochondrial damage were decreased for conditional MCU knockout mice...
May 22, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29789202/relationship-between-prolonged-neural-suppression-and-cerebral-hemodynamic-dysfunction-during-hypothermia-in-asphyxiated-piglets
#11
Wataru Jinnai, Shinji Nakamura, Kosuke Koyano, Satoshi Yamato, Takayuki Wakabayashi, Yinmon Htun, Yasuhiro Nakao, Takashi Iwase, Makoto Nakamura, Saneyuki Yasuda, Masaki Ueno, Takanori Miki, Takashi Kusaka
OBJECTIVES: Hypothermia (HT) improves the outcome of neonatal hypoxic-ischemic encephalopathy. Here, we investigated changes during HT in cortical electrical activity using amplitude-integrated electroencephalography (aEEG) and in cerebral blood volume (CBV) and cerebral hemoglobin oxygen saturation using near-infrared time-resolved spectroscopy (TRS) and compared the results with those obtained during normothermia (NT) after a hypoxic-ischemic (HI) insult in a piglet model of asphyxia...
May 19, 2018: Brain & Development
https://www.readbyqxmd.com/read/29789086/acute-mild-hypoxic-hypoxia-effects-on-cognitive-and-simulated-aircraft-pilot-performance
#12
Fethi Bouak, Oshin Vartanian, Kevin Hofer, Bob Cheung
BACKGROUND: The effects of acute mild hypoxic hypoxia (HH) and physical activity on physiological measures, signs and symptoms, mood, fatigue, cognition, and performance on a simulated flight task were investigated between 8000 (8K; 2438 m) and 14,000 ft (14K; 4267 m). METHOD: In a hypobaric chamber, 16 military helicopter pilots were randomly exposed to 4 altitudes and 3 physical exertion levels. After each exercise period, participants identified targets on a designated flight path on a desktop simulator and completed a cognitive test battery...
June 1, 2018: Aerospace Medicine and Human Performance
https://www.readbyqxmd.com/read/29789056/the-six-hour-window-how-the-community-hospital-nursery-can-optimize-outcomes-of-the-infant-with-suspected-hypoxic-ischemic-encephalopathy
#13
Dafina Ibrani, Shanon Molacavage
Perinatal hypoxia is a devastating event before, during, or immediately after birth that deprives an infant's vital organs of oxygen. This injury at birth often requires a complex resuscitation and increases the newborn's risk of hypoxic-ischemic encephalopathy (HIE). The resuscitation team in a community hospital nursery may have less experience with complex resuscitation and post-resuscitation care of this infant than a NICU. This article provides the neonatal nurse in a Level I or Level II nursery with information about resuscitation and post-resuscitation care of an infant at risk of HIE while awaiting transport to a NICU for therapeutic cooling...
May 1, 2018: Neonatal Network: NN
https://www.readbyqxmd.com/read/29788889/targeting-key-transporters-in-tumor-glycolysis-as-a-novel-anticancer-strategy
#14
Yunli Shi, Shengnan Liu, Shabir Ahmad, Qingzhi Gao
Increased glycolysis has been one of the metabolic characteristics known as the Warburg effect. The functional and therapeutic importance of the Warburg effect in targeted therapy is scientifically recognized and the glucose metabolic pathway has become a desirable target of anticancer strategies. Glucose transporters (GLUTs) play an important role in cancer glycolysis to sustain cancer cell proliferation, metastasis and survival. Utilizing the knowledge of differential expression and biological functions of GLUTs offers us the possibility of designing and delivering chemotherapeutics toward targeted tumor tissues for improved cancer selectivity...
May 22, 2018: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/29787762/hypoxic-glioblastoma-release-exosomal-vegf-a-induce-the-permeability-of-blood-brain-barrier
#15
Chen Zhao, Hongyan Wang, Chenghao Xiong, Yu Liu
Exosomes are nano-vesicles released by tumor cells to modulate extracellular environment. Accumulating evidence revealed that glioblastoma derived exosomes contain multiple pro-angiogenic factors to induce the proliferation of endothelial cells. Here, we investigated the role of GBM-derived exosomes in inducing the permeability of the blood-brain barrier. We found that VEGF-A was over-expressed in hypoxic GBM-derived exosomes, which enhance the permeability of a BBB in vitro model by interrupting the expression of claudin-5 and occludin...
May 19, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29786753/hypoxia%C3%A2-induced-expression-of-cxcr4-favors-trophoblast-cell-migration-and-invasion-via-the-activation-of-hif%C3%A2-1%C3%AE
#16
Zhan Zhang, Pengyun Li, Yan Wang, Huan Yan
The placenta initially develops in a low‑oxygen environment up to week 8‑10 of gestation, and a low oxygen level is a critical factor in the regulation of trophoblast migration and invasion. CXC chemokine receptor 4 (CXCR4) is transcriptionally activated by hypoxia in cancer cells. However, whether CXCR4 is involved in hypoxia‑inducible factor (HIF)‑1α‑dependent trophoblastic migration and invasion in a physiologically hypoxic environment (3% O2) remains to be fully elucidated and requires further investigation...
May 22, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29786420/bacteria-driven-hypoxia-targeting-for-combined-biotherapy-and-photothermal-therapy
#17
Wenfei Chen, Ying Wang, Ming Qin, Xudong Zhang, Zhirong Zhang, Xun Sun, Zhen Gu
The facultative anaerobe Salmonella strain VNP20009 selectively colonizes into tumors following systemic injection due to its preference for the hypoxia in the tumor cores. However, the Phase 1 Clinical Trial of VNP20009 has been terminated mainly due to its weak anti-tumor effects and exhibition of dose-dependent toxicity. Here we leveraged the advantages of VNP20009 biotherapy together with polydopamine-mediated photothermal therapy in order to enhance the antitumor efficacy toward malignant melanoma. VNP20009 was coated with polydopamine via oxidation and self-polymerization, which was then injected into tumor-bearing mice via the tail vein...
May 22, 2018: ACS Nano
https://www.readbyqxmd.com/read/29786141/an-inhibitory-antibody-targeting-carbonic-anhydrase-xii-abrogates-chemoresistance-and-significantly-reduces-lung-metastases-in-an-orthotopic-breast-cancer-model-in-vivo
#18
Bettina von Neubeck, Gabor Gondi, Chiara Riganti, Chenchen Pan, Arnaldo Parra Damas, Hagen Scherb, Ali Ertürk, Reinhard Zeidler
Carbonic Anhydrase XII (CAXII) is a membrane-tethered ectoenzyme involved in intracellular pH regulation and overexpressed across various types of human cancer. Because CAXII inhibition shows antitumour activity in vitro, it is thought that the enzyme is mandatory for maximum tumour growth, above all under hypoxic conditions. Recently, it has been shown that CAXII is co-expressed along with the P-glycoprotein (P-GP) on many tumour cells and that both proteins physically interact. Of interest, blocking CAXII activity also decreases P-GP activity in cancer cells both in vitro and in vivo...
May 22, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29785989/cerebral-visual-impairment-in-children-causes-and-associated-ophthalmological-problems
#19
Niranjan Pehere, Pratik Chougule, Gordon N Dutton
Purpose: The aim of this study is to identify common causes, associated ophthalmological abnormalities, and systemic comorbidities in children in Andhra Pradesh, India, with cerebral visual impairment (CVI). Methods: A retrospective review of case records of all children aged <16 years with diagnosis of CVI seen between January 2016 and December 2016 was carried out. Data were collected for their age, gender, cause of CVI, refraction, accommodation, anterior and posterior segment examination findings, and systemic problems...
June 2018: Indian Journal of Ophthalmology
https://www.readbyqxmd.com/read/29785943/-roles-and-molecular-mechanisms-of-hypoxia-inducible-factors-in-renal-cell-carcinoma
#20
Jun Xia Zou, Ke Chen
Renal cancer is a common urologic malignancy. However, the therapeutic options for metastatic renal cancer patients are limited. Hypoxia (low oxygen) is a fundamental microenvironmental determinant of solid tumor pathophysiology. Recent data from molecular and clinical studies indicate that hypoxia-inducible factors (HIFs) play critical roles in the development and progress of renal cell carcinoma (RCC). The HIF transcription factor family is a type of heterodimeric transcription factor consisting of HIF-α and HIF-β subunits and can transcriptionally activate genes that mediate the hypoxic response...
May 20, 2018: Yi Chuan, Hereditas
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