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Yan Xu, Yawei Xing, Yanjie Xu, Chahua Huang, Huihui Bao, Kui Hong, Xiaoshu Cheng
We know that silencing Bim, a pro-apoptosis protein, significantly attenuates glucose and oxygen-deprived induced apoptosis in cardiomyocytes. However, the mechanisms underlying the regulation of the Bim activation in the heart have remained unknown. Pim-2 is one of three Pim serine/threonine kinase family members thought to be involved in cell survival and proliferation. H9c2 cardiomyocytes were subjected to a hypoxia/reoxygenation (H/R) condition in vitro, mimicking ischemic/reperfusion injury in vivo. H/R augmented the expression of Bim, Cyt C, and Pim-2 and induced H9c2 cell apoptosis...
October 17, 2016: Environmental Toxicology and Pharmacology
Patrick R Arsenault, Daisheng Song, Marian Bergkamp, Andrew M Ravaschiere, Bradleigh E Navalsky, Paul M Lieberman, Frank S Lee
The Prolyl Hydroxylase Domain protein (PHD):Hypoxia Inducible Factor (HIF) pathway is the main pathway by which changes in oxygen concentration are transduced to changes in gene expression. In mammals, there are three PHD paralogues, and PHD2 has emerged as a particularly critical one for regulating HIF target genes such as ERYTHROPOIETIN (EPO), which controls red cell mass and hematocrit. PHD2 is distinctive among the three PHDs in that it contains an N-terminal MYND type zinc finger. We have proposed that this zinc finger binds a Pro-Xaa-Leu-Glu (PXLE) motif found in proteins of the HSP90 pathway to facilitate HIF-α hydroxylation...
October 22, 2016: Chembiochem: a European Journal of Chemical Biology
Danielle E Jenkins, Dharshini Sreenivasan, Fiona Carman, Samal Babru, Lee E Eiden, Stephen J Bunn
The pro-inflammatory cytokines, tumor necrosis factor-α and interleukin-1β/α modulate catecholamine secretion, and long-term gene regulation, in chromaffin cells of the adrenal medulla. Since interleukin-6 (IL6) also plays a key integrative role during inflammation, we have examined its ability to affect both tyrosine hydroxylase activity and adrenomedullary gene transcription in cultured bovine chromaffin cells. IL6 caused acute tyrosine/threonine phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), and serine/tyrosine phosphorylation of signal transducer and activator of transcription 3 (STAT3)...
October 22, 2016: Journal of Neurochemistry
Hung-Yi Liu, Tanja Greene, Tsai-Yu Lin, Camron S Dawes, Murray Korc, Chien-Chi Lin
: The complex network of biochemical and biophysical cues in the pancreatic desmoplasia not only presents challenges to the fundamental understanding of tumor progression, but also hinders the development of therapeutic strategies against pancreatic cancer. Residing in the desmoplasia, pancreatic stellate cells (PSCs) are the major stromal cells affecting the growth and metastasis of pancreatic cancer cells by means of paracrine effects and extracellular matrix protein deposition. PSCs remain in a quiescent/dormant state until they are 'activated' by various environmental cues...
October 18, 2016: Acta Biomaterialia
Dongdong Chai, Hong Jiang, Qifang Li
OBJECTIVE: Previously, we found that the inhaled anesthetic isoflurane up-regulated the transcriptional factor hypoxia inducible factor (HIF)-1α protein levels during induction of neurodegeneration in the brain of neonatal rats. Here, we investigated the role of HIF-1α and the underlying signaling pathway in the neurodegenration induced by isoflurane in rodent developing brain. METHODS: Primary hippocampal neurons were exposed to isoflurane (0.4mM) for 12h. Neuron injury was analyzed by 3-(4,5-dimethyithiazol-2-yl)-2,5-diphenyl-tetra-zolium bromide (MTT) test and quantification of lactate dehydrogenaserelease...
October 18, 2016: Brain Research
Vanessa D Ortiz, Alexandre L de Castro, Cristina Campos, Rafael O Fernandes, Jéssica H P Bonetto, Rafaela Siqueira, Adriana Conzatti, Tânia R G Fernandes, Adriane Belló-Klein, Alex S R Araujo
Studies have shown a cardioprotective role of thyroid hormones (THs) in cardiac remodeling after acute myocardial infarction (MI). However, there is no data in the literature examining the influence of TH administration on the aortic tissue in an animal model of MI. This study aimed to evaluate the effects of thyroid hormones on the aorta after MI. Male Wistar rats were divided into a sham group (SHAM), infarcted group (AMI), sham+TH (SHAMT) and AMI+TH (AMIT). After MI, the animals received T3 and T4 (2 and 8μg/100g/day, respectively) by oral gavage for 12 days...
October 18, 2016: European Journal of Pharmacology
Guosheng Song, Chenghong Ji, Chao Liang, Xuejiao Song, Xuan Yi, Ziliang Dong, Kai Yang, Zhuang Liu
Cancer radiotherapy (RT) is a clinically used tumor treatment strategy applicable for a wide range of solid tumors. However, during RT treatment of tumors, only a small portion of applied ionizing irradiation energy is absorbed by the tumor, in which the largely hypoxic microenvironment also limits the anti-tumor efficacy of RT. In this work, we rationally fabricate polyethylene glycol (PEG) stabilized perfluorocarbon (PFC) nano-droplets decorated with TaOx nanoparticles (TaOx@PFC-PEG) as a multifunctional RT sensitizer...
October 11, 2016: Biomaterials
Anna Chung-Kwan Tse, Jing-Woei Li, Simon Yuan Wang, Ting-Fung Chan, Keng Po Lai, Rudolf Shiu-Sun Wu
Hypoxia is a global environmental concern and poses a significant threat to aquatic ecosystems, including the sustainability of natural fish populations. The deleterious effects of hypoxia on fish reproductive fitness, as mediated by disruption of sex hormones and gene expression along the Brain-Pituitary-Gonad axis, have been well documented. Recently, we further demonstrated that the observed disruption of steroidogenesis in the ovary of marine medaka Oryzias melastigma is mediated through microRNAs (miRNAs)...
October 8, 2016: Aquatic Toxicology
Le My Phuong, Do Thi Thanh Huong, Jens Randel Nyengaard, Mark Bayley
Gill morphometric and gill plasticity of the air-breathing striped catfish (Pangasianodon hypophthalmus) exposed to different temperatures (present day 27°C and future 33°C) and different air saturation levels (92% and 35%) during 6weeks were investigated using vertical sections to estimate the respiratory lamellae surface areas, harmonic mean barrier thicknesses, and gill component volumes. Gill respiratory surface area (SA) and harmonic mean water - blood barrier thicknesses (HM) of the fish were strongly affected by both environmental temperature and oxygen level...
October 18, 2016: Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology
Tianwei E Zhou, José C Rivera, Vikrant K Bhosle, Isabelle Lahaie, Zhuo Shao, Houda Tahiri, Tang Zhu, Anna Polosa, Allison Dorfman, Alexandra Beaudry-Richard, Santiago Costantino, Gregory A Lodygensky, Pierre Lachapelle, Sylvain Chemtob
Retinopathy of prematurity (ROP), the most common cause of blindness in premature infants, has long been associated with inner retinal alterations. However, recent studies reveal outer retinal dysfunctions in patients formerly afflicted with ROP. We have recently demonstrated that choroidal involution occurs early in retinopathy. Herein, we investigated the mechanisms underlying the choroidal involution and its long-term impact on retinal function. An oxygen-induced retinopathy (OIR) model was used. In vitro and ex vivo assays were applied to evaluate cytotoxic effects of IL-1β on choroidal endothelium...
October 18, 2016: American Journal of Pathology
Joseph K Maddry, Alejandra G Mora, Shelia Savell, Lauren K Reeves, Crystal A Perez, Vikhyat S Bebarta
BACKGROUND: Medical evacuation (MEDEVAC) is the movement and en route care of injured and medically compromised patients by medical care providers via helicopter. Military MEDEVAC platforms provide lifesaving interventions that improve survival in combat. There is limited evidence to support decision making related to en route care and allocation of resources. The association between provider type and en route care is not well understood. Our objective was to describe MEDEVAC providers and identify associations between provider type, procedures performed, and outcomes...
November 2016: Journal of Trauma and Acute Care Surgery
Ferit Dogan, Dilek Sen Dokumaci, Ali Yildirim, Erol Bozdogan, Fatima Nurefsan Boyaci, Bulent Koca, Ekrem Karakas
OBJECTIVES: This preliminary study aimed to evaluate whether there are changes in the Apparent Diffusion Coefficient (ADC) values of the brain in patients presenting with Eisenmenger syndrome (ES). METHODS: This cross-sectional study included 10 consecutively recruited patients with ES and 10 healthy control subjects. In the patients and controls, 8 distinct neuroanatomical locations were selected for the analysis. Quantitative measurements of ADC values of the frontal and occiptal white matter, lentiform nucleus, thalamus, frontal cortex, anterior and posterior limbs of the internal capsule, caudate nucleus were measured...
October 21, 2016: British Journal of Radiology
Yun-Wen Yang, Chun-Mei Zhang, Xian-Jie Huang, Xiao-Xin Zhang, Lin-Kai Zhang, Jia-Huang Li, Zi-Chun Hua
Fas-associated protein with death domain (FADD), a pivotal adaptor protein transmitting apoptotic signals, is indispensable for the induction of extrinsic apoptosis. However, overexpression of FADD can form large, filamentous aggregates, termed death effector filaments (DEFs) by self-association and initiate apoptosis independent of receptor cross-linking. A mutant of FADD, which is truncated of the C-terminal tail (m-FADD, 182-205 aa) named N-FADD (m-FADD, 1-181 aa), can dramatically up-regulate the strength of FADD self-association and increase apoptosis...
October 21, 2016: Scientific Reports
Qian-Qian Luo, Zhong-Ming Qian, Yu-Fu Zhou, Meng-Wan Zhang, Dang Wang, Li Zhu, Ya Ke
The inconsistent of responses of IRP1 and HIF-1 alpha to hypoxia and the similar tendencies in the changes of IRP1 and pCREB contents led us to hypothesize that pCREB might be involved in the regulation of IRP1 under hypoxia. Here, we investigated the role of pCREB in IRP1 expression in HepG2 cells under hypoxia using quantitative PCR, western blot, immunofluorescence, electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP). We demonstrated that 1) Hypoxia increased pCREB levels inside of the nucleus; 2) Putative CREs were found in the IRP1 gene; 3) Nuclear extracts of HepG2 cells treated with hypoxia could bind to CRE1 and CRE3, and 100-fold competitor of putative CREs could abolish the binding activity to varying degrees; 4) pCREB was found in the CRE1 and CRE3 DNA-protein complexes of EMSA; 5) CRE1 and CRE3 binding activity of IRP1 depended on CREB activation but not on HIF-1; 6) Increased IRP1 expression under hypoxia could be prevented by LY294002; 7) ChIP assays demonstrated that pCREB binds to IRP1 promoter; and 8) HIF-1 and/or HIF-2 siRNA had no effect on the expression of pCREB and IRP1 proteins in cells treated with hypoxia for 8 hours...
2016: International Journal of Biological Sciences
Kevin Vivot, Malika A Benahmed, Elodie Seyfritz, William Bietiger, Karim Elbayed, Elisa Ruhland, Allan Langlois, Elisa Maillard, Michel Pinget, Nathalie Jeandidier, Jean-Pierre Gies, Izzie-Jacques Namer, Séverine Sigrist, Nathalie Reix
Intrahepatic transplantation of islets requires a lot of islets because more than 50% of the graft is lost during the 24 hours following transplantation. We analyzed, in a rat model, early post-transplantation inflammation using systemic inflammatory markers, or directly in islet-transplanted livers by immunohistochemistry. (1)H HRMAS NMR was employed to investigate metabolic responses associated with the transplantation. Inflammatory markers (Interleukin-6, α2-macroglobulin) are not suitable to follow islet reactions as they are not islet specific...
2016: International Journal of Biological Sciences
Chien-Cheng Chen, Chan-Yen Kuo, Rong-Fu Chen
Background: Cardiomyocyte under hypoxia cause cell death or damage is associated with heart failure. Gap junction, such as connexin 43 play a role in regulation of heart function under hypoxia. Caffeic acid phenethyl ester (CAPE) has been reported as an active component of propolis, has antioxidative, anti-inflammatory antiproliferative and antineoplastic biological properties. Aims: Connexin 43 appear to have a critical role in heart failure under hypoxia, there has been considerable interest in identifying the candidate component or compound to reduce cell death...
2016: International Journal of Medical Sciences
Chengxing Zhu, Jiong Yu, Qiaoling Pan, Jinfeng Yang, Guangshu Hao, Yingjie Wang, Lanjuan Li, Hongcui Cao
Human placenta-derived mesenchymal stem cells (hPMSCs) reside in a physiologically low-oxygen microenvironment. Hypoxia influences a variety of stem cell cellular activities, frequently involving hypoxia-inducible factor-2 alpha (HIF-2α). This research showed that hPMSCs cultured in hypoxic conditions (5% O2) exhibited a more naïve morphology and had a higher proliferative capability and higher HIF-2α expression than hPMSCs cultured in normoxic conditions (21% O2). Similar to the hypoxic cultures, hPMSCs over-expressing HIF-2α showed higher proliferative potential and higher expression of CCND1 (CyclinD1), MYC (c-Myc), POU5F1 (Oct4) and the components of the MAPK/ERK pathway...
October 21, 2016: Scientific Reports
Mark A Applebaum, Aashish R Jha, Clara Kao, Kyle M Hernandez, Gillian DeWane, Helen R Salwen, Alexandre Chlenski, Marija Dobratic, Christopher J Mariani, Lucy A Godley, Nanduri Prabhakar, Kevin White, Barbara E Stranger, Susan L Cohn
Neuroblastoma is notable for its broad spectrum of clinical behavior ranging from spontaneous regression to rapidly progressive disease. Hypoxia is well known to confer a more aggressive phenotype in neuroblastoma. We analyzed transcriptome data from diagnostic neuroblastoma tumors and hypoxic neuroblastoma cell lines to identify genes whose expression levels correlate with poor patient outcome and are involved in the hypoxia response. By integrating a diverse set of transcriptome datasets, including those from neuroblastoma patients and neuroblastoma derived cell lines, we identified nine genes (SLCO4A1, ENO1, HK2, PGK1, MTFP1, HILPDA, VKORC1, TPI1, and HIST1H1C) that are up-regulated in hypoxia and whose expression levels are correlated with poor patient outcome in three independent neuroblastoma cohorts...
October 17, 2016: Oncotarget
David Rizo-Roca, Juan Gabriel Ríos-Kristjánsson, Cristian Núñez-Espinosa, Estela Santos-Alves, Ines O Goncalves, Jose Magalhaes, Antonio A Ascensao, Teresa Pagès, Ginés Viscor, Joan Ramon Torrella
Unaccustomed eccentric exercise leads to muscle morphological and functional alterations, including microvasculature damage, the repair of which is modulated by hypoxia. Here we present the effects of intermittent hypobaric hypoxia and exercise on recovery from eccentric-induced muscle damage (EEIMD). Soleus muscles from trained rats were excised pre- (CTRL) and 1, 3, 7 and 14 days after a double session of EEIMD protocol. A recovery treatment consisting of one of the following protocols was applied one day after the EEIMD: passive normobaric recovery (PNR), a 4-hour daily exposure to passive hypobaric hypoxia at 4000m (PHR) or hypobaric hypoxia exposure followed by aerobic exercise (AHR)...
October 20, 2016: Journal of Applied Physiology
William Spencer Cheyne, Alexandra Mackenzie Williams, Megan Harper, Neil Derek Eves
COPD is associated with dynamic lung hyperinflation (DH), increased pulmonary vascular resistance (PVR) and large increases in negative intrathoracic pressure (nITP). The individual and interactive effect of these stressors on left ventricular (LV) filling, emptying and geometry, and the role of direct ventricular interaction (DVI) in mediating these interactions have not been fully elucidated. Twenty healthy subjects were exposed to the following stressors alone and in combination: 1) inspiratory resistive loading of -20 cmH2O (nITP), 2) expiratory resistive loading to cause dynamic hyperinflation (DH), and 3) normobaric-hypoxia to increase PVR (hPVR)...
October 7, 2016: American Journal of Physiology. Heart and Circulatory Physiology
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