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https://www.readbyqxmd.com/read/28629892/engineered-myocardium-model-to-study-the-roles-of-hif-1%C3%AE-and-hif1a-as1-in-paracrine-only-signaling-under-pathological-level-oxidative-stress
#1
Aylin Acun, Pinar Zorlutuna
Studying heart tissue is critical for understanding and developing treatments for cardiovascular diseases. In this work, we fabricated precisely controlled and biomimetic engineered model tissues to study how cell-cell and cell-matrix interactions influence myocardial cell survival upon exposure to pathological level oxidative stress. Specifically, the interactions of endothelial cells (ECs) and cardiomyocytes (CMs), and the role of hypoxia inducible factor-1α (HIF-1α), with its novel alternative regulator, HIF-1α antisense RNA1 (HIF1A-AS1), in these interactions were investigated...
June 16, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28623968/oxygen-and-tissue-culture-affect-placental-gene-expression
#2
O Brew, M H F Sullivan
INTRODUCTION: Placental explant culture is an important model for studying placental development and functions. We investigated the differences in placental gene expression in response to tissue culture, atmospheric and physiologic oxygen concentrations. METHODS: Placental explants were collected from normal term (38-39 weeks of gestation) placentae with no previous uterine contractile activity. Placental transcriptomic expressions were evaluated with GeneChip(®) Human Genome U133 Plus 2...
July 2017: Placenta
https://www.readbyqxmd.com/read/28620317/comparative-and-experimental-studies-on-the-genes-altered-by-chronic-hypoxia-in-human-brain-microendothelial-cells
#3
Eugenia Mata-Greenwood, Dipali Goyal, Ravi Goyal
Background : Hypoxia inducible factor 1 alpha (HIF1A) is a master regulator of acute hypoxia; however, with chronic hypoxia, HIF1A levels return to the normoxic levels. Importantly, the genes that are involved in the cell survival and viability under chronic hypoxia are not known. Therefore, we tested the hypothesis that chronic hypoxia leads to the upregulation of a core group of genes with associated changes in the promoter DNA methylation that mediates the cell survival under hypoxia. Results : We examined the effect of chronic hypoxia (3 days; 0...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28614042/bnip3l-nix-dependent-mitophagy-regulates-cell-differentiation-via-metabolic-reprogramming
#4
Lorena Esteban-Martínez, Patricia Boya
Macroautophagy/autophagy is the process by which cellular components are degraded and recycled within the lysosome. These components include mitochondria, the selective degradation of which is known as mitophagy. Mitochondria are dynamic organelles that constantly adapt their morphology, function, and number to accommodate the metabolic needs of the cell. Extensive metabolic reconfiguration occurs during cell differentiation, when mitochondrial activity increases in most cell types. However, our data demonstrate that during physiological retinal ganglion cell (RGC) development, mitophagy-dependent metabolic reprogramming towards glycolysis regulates numbers of RGCs, which are the first neurons to differentiate in the retina and whose axons form the optic nerve...
June 14, 2017: Autophagy
https://www.readbyqxmd.com/read/28607111/a-distinct-inhibitory-function-for-mir-18a-in-th17-cell-differentiation
#5
Misty M Montoya, Julia Maul, Priti B Singh, Heather H Pua, Frank Dahlström, Nanyan Wu, Xiaozhu Huang, K Mark Ansel, Dirk Baumjohann
Th17 cell responses orchestrate immunity against extracellular pathogens but also underlie autoimmune disease pathogenesis. In this study, we uncovered a distinct and critical role for miR-18a in limiting Th17 cell differentiation. miR-18a was the most dynamically upregulated microRNA of the miR-17-92 cluster in activated T cells. miR-18a deficiency enhanced CCR6(+) RAR-related orphan receptor (ROR)γt(+) Th17 cell differentiation in vitro and increased the number of tissue Th17 cells expressing CCR6, RORγt, and IL-17A in airway inflammation models in vivo...
June 12, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28595632/a-comparison-of-gene-expression-profiles-in-patients-with-coronary-artery-disease-type-2-diabetes-and-their-coexisting-conditions
#6
Rui Gong, Menghui Chen, Cuizhao Zhang, Manli Chen, Haibin Li
BACKGROUND: To support a hypothesis that there is an intrinsic interplay between coronary artery disease (CAD) and type 2 diabetes (T2D), we used RNA-seq to identify unique gene expression signatures of CAD, T2D, and coexisting conditions. METHODS: After transcriptome sequencing, differential expression analysis was performed between each disordered state and normal control group. By comparing gene expression profiles of CAD, T2D, and coexisting conditions, common and specific patterns of each disordered state were displayed...
June 8, 2017: Diagnostic Pathology
https://www.readbyqxmd.com/read/28573109/persistence-of-innate-immune-pathways-in-late-stage-human-bacterial-and-fungal-keratitis-results-from-a-comparative-transcriptome-analysis
#7
Jaya D Chidambaram, Shichina Kannambath, Palepu Srikanthi, Manisha Shah, Prajna Lalitha, Shanmugam Elakkiya, Julien Bauer, Namperumalsamy V Prajna, Martin J Holland, Matthew J Burton
Microbial keratitis (MK) is a major cause of blindness worldwide. Despite adequate antimicrobial treatment, tissue damage can ensue. We compared the human corneal transcriptional profile in late stage MK to normal corneal tissue to identify pathways involved in pathogenesis. Total RNA from MK tissue and normal cadaver corneas was used to determine transcriptome profiles with Illumina HumanHT-12 v4 beadchips. We performed differential expression and network analysis of genes in bacterial keratitis (BK) and fungal keratitis (FK) compared with control (C) samples...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28558704/genome-wide-network-based-pathway-analysis-of-csf-t-tau-a%C3%AE-1-42-ratio-in-the-adni-cohort
#8
Wang Cong, Xianglian Meng, Jin Li, Qiushi Zhang, Feng Chen, Wenjie Liu, Ying Wang, Sipu Cheng, Xiaohui Yao, Jingwen Yan, Sungeun Kim, Andrew J Saykin, Hong Liang, Li Shen
BACKGROUND: The cerebrospinal fluid (CSF) levels of total tau (t-tau) and Aβ1-42 are potential early diagnostic markers for probable Alzheimer's disease (AD). The influence of genetic variation on these CSF biomarkers has been investigated in candidate or genome-wide association studies (GWAS). However, the investigation of statistically modest associations in GWAS in the context of biological networks is still an under-explored topic in AD studies. The main objective of this study is to gain further biological insights via the integration of statistical gene associations in AD with physical protein interaction networks...
May 30, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28543639/lncrna-rp11-296a18-3-mir-138-hif1a-pathway-regulates-the-proliferation-ecm-synthesis-of-human-nucleus-pulposus-cells-hnpcs-%C3%A2
#9
Xiaobin Wang, Guohua Lv, Jing Li, Bing Wang, Qianshi Zhang, Chang Lu
BACKGROUND: During the process of Intervertebral disc degeneration (IDD), nucleus pulposus apoptosis increases, extracellular matrix (ECM) alters and/or degrades, abnormal proliferation of cells forms cell clusters, and the expression of various inflammatory factors increases. Thus, regulation of human nucleus pulposus cell (HNPC) proliferation and ECM synthesis present promising strategies for IDD treatment. Accumulating evidence indicates that non-coding RNAs are involved in various cellular processes, including cell proliferation, differentiation, apoptosis and metastasis...
May 24, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28527294/activation-of-hypoxia-signaling-in-stromal-progenitors-impairs-kidney-development
#10
Katharina Gerl, Dominik Steppan, Michaela Fuchs, Charlotte Wagner, Carsten Willam, Armin Kurtz, Birgül Kurt
Intrauterine hypoxia is a reason for impaired kidney development. The cellular and molecular pathways along which hypoxia exerts effects on nephrogenesis are not well understood. They are likely triggered by hypoxia-inducible transcription factors (HIFs), and their effects appear to be dependent on the cell compartment contributing to kidney formation. In this study, we investigated the effects of HIF activation in the developing renal stroma, which also essentially modulates nephron development from the metanephric mesenchyme...
July 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28522586/antitumor-synergism-and-enhanced-survival-with-a-tumor-vasculature-targeted-enzyme-prodrug-system-rapamycin-and-cyclophosphamide
#11
John J Krais, Needa Virani, Partick H McKernan, Quang Nguyen, Kar-Ming Fung, Vassilios I Sikavitsas, Carla D Kurkjian, Roger G Harrison
Mutant cystathionine gamma-lyase was targeted to phosphatidylserine exposed on tumor vasculature through fusion with annexin A1 or annexin A5.  Cystathionine gamma-lyase E58N, R118L, and E338N mutations impart non-native methionine gamma-lyase activity, resulting in tumor-localized generation of highly toxic methylselenol upon systemic administration of non-toxic selenomethionine.  The described therapeutic system circumvents systemic toxicity issues using a novel drug delivery/generation approach and avoids the administration of non-native proteins and/or DNA required with other enzyme prodrug systems...
May 18, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28506076/nos2-as-an-emergent-player-in-progression-of-cancer
#12
Douglas D Thomas, David A Wink
Although the inducible form of nitric oxide synthase (NOS2) was initially shown to be a major player as an antitumor component of the immune response, more recent data have shown that NOS2 expression in cancer cells often predicts poor outcome. Unlike growth factors associated with a single oncogenic pathway, nitric oxide (NO) has a ubiquitous nature wherein it simultaneously mediates major oncogenic pathways from Akt/PI3K and RAS/ERK to HIF1a and TGFb. These interactive loops perpetuate oncogenic mechanism that leads to increased cancer stemness, proliferation metastasis, chemoresistance, angiogenesis, and immunosuppression...
June 10, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28493484/cytoplasmic-overexpression-of-rna-binding-protein-hur-is-a-marker-of-poor-prognosis-in-meningioma-and-hur-knockdown-decreases-meningioma-cell-growth-and-resistance-to-hypoxia
#13
Guillaume Gauchotte, Sébastien Hergalant, Charlène Vigouroux, Jean-Matthieu Casse, Rémi Houlgatte, Tony Kaoma, Déborah Helle, Lydia Brochin, Fabien Rech, Matthieu Peyre, François Labrousse, Laurent Vallar, Jean-Louis Gueant, Jean-Michel Vignaud, Shyue-Fang Battaglia-Hsu
HuR regulates cytoplasmic mRNA stability and translatability, and the HuR expression level has been shown to correlate with poor disease outcome in several cancer types; however, the prognostic value and potential pro-oncogenic properties of HuR in meningioma remain unclear. Thus, in the present study we analyzed 85 meningioma tissue samples to establish the relationship between HuR expression, tumor-cell proliferation, and/or patient survival. In addition, we examined the anti-proliferative effects of HuR knockdown in two meningioma cell lines (IOMM-Lee and Ben-Men1), and conducted transcriptome-wide analyses (IOMM-Lee cells) to elucidate the molecular consequences of HuR knockdown...
May 11, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28484714/hif1a-rs11549465-and-akna-rs10817595-gene-polymorphisms-are-associated-with-primary-sj%C3%A3-gren-s-syndrome
#14
Gabriela Hernández-Molina, José Manuel Rodríguez-Pérez, Javier Fernández-Torres, Guadalupe Lima, Nonanzit Pérez-Hernández, Alberto López-Reyes, Gabriela Angélica Martínez-Nava
Objective. To evaluate the allele and genotype frequencies of polymorphic sites of HIF1A and ANKA genes in primary Sjögren's syndrome (pSS). Methods. We included 110 patients with pSS and 141 ethnically matched healthy controls. Three HIF1A gene polymorphisms (Pro582Ser, Ala588Thr, and C191T) and two AKNA gene polymorphisms (-1372C>A and Pro624Leu) were genotyped using TaqMan probes in a Real-Time PCR instrument. Associations between pSS and genotypes, alleles, and inheritance models of the SNPs of interest were evaluated by logistic regression adjusted by age and gender...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28476527/hypoxia-and-renal-cell-carcinoma-the-influence-of-hif1a-1772c-t-functional-genetic-polymorphism-on-prognosis
#15
Marta Ferreira, Ana Teixeira, Joaquina Maurício, Francisco Lobo, António Morais, Rui Medeiros
OBJECTIVES: Hypoxia-inducible factor (HIF-1) is a key regulator of the genes involved in the cellular response to hypoxia. Overexpression of HIF-1 has been implicated in the pathogenesis of renal cell carcinoma (RCC), and functional polymorphisms of the HIF1A gene may confer susceptibility to RCC. Our purpose was to assess the influence of HIF1A+1772C/T (rs11549465) polymorphism on RCC prognosis. MATERIAL AND METHODS: This study evaluated the associations of the HIF1A+1772C/T (rs11549465) polymorphism with clinicopathologic prognostic factors, recurrence/progression, and survival in a cohort of 179 patients with RCC treated at Portuguese Oncology Institute of Porto...
May 2, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/28437727/new-inter-correlated-genes-targeted-by-diatom-derived-polyunsaturated-aldehydes-in-the-sea-urchin-paracentrotus-lividus
#16
Nadia Ruocco, Anna Maria Fedele, Susan Costantini, Giovanna Romano, Adrianna Ianora, Maria Costantini
The marine environment is continually subjected to the action of stressors (including natural toxins), which represent a constant danger for benthic communities. In the present work using network analysis we identified ten genes on the basis of associated functions (FOXA, FoxG, GFI-1, nodal, JNK, OneCut/Hnf6, TAK1, tcf4, TCF7, VEGF) in the sea urchin Paracentrotus lividus, having key roles in different processes, such as embryonic development and asymmetry, cell fate specification, cell differentiation and morphogenesis, and skeletogenesis...
August 2017: Ecotoxicology and Environmental Safety
https://www.readbyqxmd.com/read/28435028/antagonistic-effects-of-p53-and-hif1a-on-microrna-34a-regulation-of-ppp1r11-and-stat3-and-hypoxia-induced-epithelial-to-mesenchymal-transition-in-colorectal-cancer-cells
#17
Huihui Li, Matjaz Rokavec, Longchang Jiang, David Horst, Heiko Hermeking
BACKGROUND & AIMS: In colorectal tumors, hypoxia causes resistance to therapy and promotes metastasis. Loss of the tumor suppressor p53 (encoded by TP53) provides cancer cells with a selective advantage under conditions of hypoxia, but little is known about the mediators of this effect. METHODS: Isogenic colorectal cancer (CRC) cell lines with different TP53 genotypes were placed under conditions of hypoxia. We examined the effects on levels and activity of microRNA-34a (MIR34A) in CRC cells...
April 20, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28430666/myc-induced-glutaminolysis-bypasses-hif-driven-glycolysis-in-hypoxic-small-cell-lung-carcinoma-cells
#18
Matilda Munksgaard Thorén, Marica Vaapil, Johan Staaf, Maria Planck, Martin E Johansson, Sofie Mohlin, Sven Påhlman
We previously demonstrated that small cell lung carcinoma (SCLC) cells lack HIF-2α protein expression, whereas HIF-1α in these cells is expressed at both acute and prolonged hypoxia. Here we show that low HIF2A expression correlates with high expression of MYC genes. Knockdown of HIF1A expression had no or limited effect on cell survival and growth in vitro. Unexpectedly, hypoxic ATP levels were not affected by HIF-1α knockdown and SCLC cell viability did not decrease upon glucose deprivation. In line with these in vitro data, xenograft tumor-take and growth were not significantly affected by repressed HIF1A expression...
April 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423608/anthracyclines-suppress-pheochromocytoma-cell-characteristics-including-metastasis-through-inhibition-of-the-hypoxia-signaling-pathway
#19
Ying Pang, Chunzhang Yang, Jan Schovanek, Herui Wang, Petra Bullova, Veronika Caisova, Garima Gupta, Katherine I Wolf, Gregg L Semenza, Zhengping Zhuang, Karel Pacak
Pheochromocytomas (PHEOs) and paragangliomas (PGLs) are rare, neuroendocrine tumors derived from adrenal or extra-adrenal chromaffin cells, respectively. Metastases are discovered in 3-36% of patients at the time of diagnosis. Currently, only suboptimal treatment options exist. Therefore, new therapeutic compounds targeting metastatic PHEOs/PGLs are urgently needed. Here, we investigated if anthracyclines were able to suppress the progression of metastatic PHEO. We explored their effects on experimental mouse PHEO tumor cells using in vitro and in vivo models, and demonstrated that anthracyclines, particularly idarubicin (IDA), suppressed hypoxia signaling by preventing the binding of hypoxia-inducible factor 1 and 2 (HIF-1 and HIF-2) to the hypoxia response element (HRE) sites on DNA...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28417167/gene-expression-levels-of-gamma-glutamyl-hydrolase-in-tumor-tissues-may-be-a-useful-biomarker-for-the-proper-use-of-s-1-and-tegafur-uracil-leucovorin-in-preoperative-chemoradiotherapy-for-patients-with-rectal-cancer
#20
Sotaro Sadahiro, T Suzuki, A Tanaka, K Okada, G Saito, H Miyakita, T Ogimi, H Nagase
PURPOSE: Preoperative chemoradiotherapy (CRT) using 5-fluorouracil (5-FU)-based chemotherapy is the standard of care for rectal cancer. The effect of additional chemotherapy during the period between the completion of radiotherapy and surgery remains unclear. Predictive factors for CRT may differ between combination chemotherapy with S-1 and with tegafur-uracil/leucovorin (UFT/LV). METHODS: The subjects were 54 patients with locally advanced rectal cancer who received preoperative CRT with S-1 or UFT/LV...
June 2017: Cancer Chemotherapy and Pharmacology
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