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https://www.readbyqxmd.com/read/28641336/suppression-of-forkhead-box-protein-o1-foxo1-transcription-factor-may-promote-adrenocortical-tumorigenesis
#1
Adam Stenman, Timothy Murtha, Reju Korah, Tobias Carling
Despite recent comprehensive genetic analyses, molecular evidence for a pathophysiological continuum linking benign adrenocortical adenoma (ACA) and highly aggressive adrenocortical carcinoma (ACC) is still elusive. Using human tumor samples and the established ACC cell line SW-13, this study investigated potential regulatory roles for FOXO transcription factors, in modulating adrenocortical tumorigenesis. Adrenocortical tumor specimens (20 ACAs, 10 ACCs, and 9 normal adrenal tissue samples) obtained from 30 patients were analyzed for ubiquitously expressed FOXO transcription factors, FOXO1 and FOXO3 using qRT-PCR and immunohistochemistry...
June 22, 2017: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
https://www.readbyqxmd.com/read/28639090/mitochondria-and-foxo3-in-stem-cell-homeostasis-a-window-into-hematopoietic-stem-cell-fate-determination
#2
Raymond Liang, Saghi Ghaffari
The production of all blood cells from hematopoietic stem cells (HSC) is highly sensitive to reactive oxygen species (ROS). Cumulating evidence suggests that mitochondria are critical for HSC fate determination. FOXO are known regulators of anti-oxidant response and key to the maintenance of HSC. Recent works indicate that FOXO3 is implicated in the control of mitochondrial function beyond regulating levels of ROS in HSC. Here we review these findings and discuss implications for homeostatic blood formation and stem cell fate determination...
June 21, 2017: Journal of Bioenergetics and Biomembranes
https://www.readbyqxmd.com/read/28638078/the-stress-response-factor-daf-16-foxo-is-required-for-multiple-compound-families-to-prolong-the-function-of-neurons-with-huntington-s-disease
#3
Francesca Farina, Emmanuel Lambert, Lucie Commeau, François-Xavier Lejeune, Nathalie Roudier, Cosima Fonte, J Alex Parker, Jacques Boddaert, Marc Verny, Etienne-Emile Baulieu, Christian Neri
Helping neurons to compensate for proteotoxic stress and maintain function over time (neuronal compensation) has therapeutic potential in aging and neurodegenerative disease. The stress response factor FOXO3 is neuroprotective in models of Huntington's disease (HD), Parkinson's disease and motor-neuron diseases. Neuroprotective compounds acting in a FOXO-dependent manner could thus constitute bona fide drugs for promoting neuronal compensation. However, whether FOXO-dependent neuroprotection is a common feature of several compound families remains unknown...
June 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28636549/p53-independent-p21-induction-by-melk-inhibition
#4
Tatsuo Matsuda, Taigo Kato, Kazuma Kiyotani, Yunus Emre Tarhan, Vassiliki Saloura, Suyoun Chung, Koji Ueda, Yusuke Nakamura, Jae-Hyun Park
MELK play critical roles in human carcinogenesis through activation of cell proliferation, inhibition of apoptosis and maintenance of stemness. Therefore, MELK is a promising therapeutic target for a wide range of cancers. Although p21 is a well-known p53-downstream gene, we found that treatment with a potent MELK inhibitor, OTS167, could induce p21 protein expression in cancer cell lines harboring loss-of-function TP53 mutations. We also confirmed that MELK knockdown by siRNA induced the p21 expression in p53-deficient cancer cell lines and caused the cell cycle arrest at G1 phase...
June 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28627974/microrna-132-protects-hippocampal-neurons-against-oxygen-glucose-deprivation-induced-apoptosis
#5
Zu-Zhen Sun, Zhan-Yun Lv, Wen-Jing Tian, Yan Yang
Hypoxic-ischemic brain injury (HIBI) results in death or long-term neurologic impairment in both adults and children. In this study, we investigated the effects of microRNA-132 (miR-132) dysregulation on oxygen-glucose deprivation (OGD)-induced apoptosis in fetal rat hippocampal neurons, in order to reveal the therapeutic potential of miR-132 on HIBI. MiR-132 dysregulation was induced prior to OGD exposure by transfection of primary fetal rat hippocampal neurons with miR-132 mimic or miR-132 inhibitor. The effects of miR-132 overexpression and suppression on OGD-stimulated hippocampal neurons were evaluated by detection of cell viability, apoptotic cells rate, and the expression of apoptosis-related proteins...
June 1, 2017: International Journal of Immunopathology and Pharmacology
https://www.readbyqxmd.com/read/28621049/lower-foxo3-mrna-expression-in-granulosa-cells-is-involved-in-unexplained-infertility
#6
Hikaru Yamamoto, Yoshiki Yamashita, Natsuho Saito, Atsushi Hayashi, Masami Hayashi, Yoshito Terai, Masahide Ohmichi
AIM: The aim of this study was to investigate whether FOXO1 and FOXO3 mRNA expression in granulosa cells is the cause of unexplained infertility. METHODS: Thirty-one patients aged <40 years (13 with unexplained infertility and 18 with male partner infertility as a control group) whose serum anti-Müllerian hormone level was >0.5 ng/μL were enrolled in the study. All patients underwent oocyte retrieval under a short protocol from June 2012 to October 2013...
June 2017: Journal of Obstetrics and Gynaecology Research
https://www.readbyqxmd.com/read/28615249/reduction-in-podocyte-sirt1-accelerates-kidney-injury-in-aging-mice
#7
Peter Y Chuang, Weijing Cai, Xuezhu Li, Lu Fang, Jin Xu, Rabi Yacoub, John Cijiang He, Kyung Lee
Both the incidence and prevalence of chronic kidney disease are increasing in the elderly population. Although aging is known to induce kidney injury, the underlying molecular mechanisms remain unclear. Sirtuin 1 (Sirt1), a longevity gene, is known to protect kidney cell injury from various cellular stresses. In previous studies, we showed that the podocyte-specific loss of Sirt1 aggravates diabetic kidney injury. However, the role of Sirt1 in aging-induced podocyte injury is not known. Therefore, in this study we sought to determine the effects of podocyte-specific reduction of Sirt1 in age-induced kidney injury...
June 14, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28615107/-preparation-and-characterization-of-mouse-polyclonal-antibody-against-conserved-region-of-human-foxo3
#8
Lei Li, Dan Lyu
Objective To purify the recombinant protein specific to conserved region of forkhead box O3 (FOXO3) and prepare mouse anti-human FOXO3 polyclonal antibody. Methods The DNA fragment (aa290-472) encoding conserved domain of FOXO3 was amplified by PCR, and subsequently cloned into pET28a vector. Following transformation into E.coli BL21, the soluble fusion protein His-FOXO3 was induced by IPTG and purified by Ni-NTA affinity chromatography. The purified protein was used to immunize BALB/c mice to generate polyclonal antibody...
June 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/28602396/mycoplasma-fermentans-deacetylase-promotes-mammalian-cell-stress-tolerance
#9
Qingzhou Cheng, Lijuan Wu, Rongfu Tu, Jun Wu, Wenqian Kang, Tong Su, Runlei Du, Wenbin Liu
Mycoplasma fermentans is a pathogenic bacterium that infects humans and has potential pathogenic roles in respiratory, genital and rheumatoid diseases. NAD(+)-dependent deacetylase is involved in a wide range of pathophysiological processes and our studies have demonstrated that expression of mycoplasmal deacetylase in mammalian cells inhibits proliferation but promotes anti-starvation stress tolerance. Furthermore, mycoplasmal deacetylase is involved in cellular anti-oxidation, which correlates with changes in the proapoptotic proteins BIK, p21 and BIM...
August 2017: Microbiological Research
https://www.readbyqxmd.com/read/28594286/peroxisomes-as-modulators-of-cellular-protein-thiol-oxidation-a-new-model-system
#10
Celien Lismont, Marcus Nordgren, Chantal Brees, Bernard Knoops, Paul P Van Veldhoven, Marc Fransen
<b><i>Aims:</i></b> Peroxisomes are ubiquitous, single membrane-bounded organelles that contain considerable amounts of enzymes involved in the production or breakdown of hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>), a key signaling molecule in multiple biological processes and disease states. Despite this, the role of this organelle in cross-compartmental H<sub>2</sub>O<sub>2</sub> signaling remains largely unclear, mainly because of the difficulty to modulate peroxisomal H<sub>2</sub>O<sub>2</sub> production in a selective manner...
June 8, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28578881/increased-myogenic-and-protein-turnover-signaling-in-skeletal-muscle-of-chronic-obstructive-pulmonary-disease-patients-with-sarcopenia
#11
Anita E M Kneppers, Ramon C J Langen, Harry R Gosker, Lex B Verdijk, Nanca Cebron Lipovec, Pieter A Leermakers, Marco C J M Kelders, Chiel C de Theije, Daniel Omersa, Mitja Lainscak, Annemie M W J Schols
BACKGROUND: Sarcopenia was recently recognized as an independent condition by an International Classification of Diseases, Tenth Revision, Clinical Modification code, and is a frequently observed comorbidity in chronic obstructive pulmonary disease (COPD). Muscle mass is primarily dictated by the balance between protein degradation and synthesis, but their relative contribution to sarcopenia is unclear. OBJECTIVE: We aimed to assess potential differential molecular regulation of protein degradation and synthesis, as well as myogenesis, in the skeletal muscle of COPD patients with and without sarcopenia...
May 31, 2017: Journal of the American Medical Directors Association
https://www.readbyqxmd.com/read/28577647/foxo3-gene-expression-and-oxidative-status-in-beta-thalassemia-minor-subjects
#12
Sandra Stella Lazarte, María Eugenia Mónaco, Magdalena María Terán, Ana Cecilia Haro, Miryam Emilse Ledesma Achem, Blanca Alicia Issé
BACKGROUND: Oxidative stress may aggravate symptoms of hemolytic anemias such as beta-thalassemia. FoxO3 activation results in resistance to oxidative stress in fibroblasts and neuronal cell cultures. OBJECTIVE: The purpose of this research was to study FoxO3 gene expression and oxidative status in beta-thalassemia minor individuals. METHODS: Sixty-three subjects (42 apparently healthy individuals and 21 with beta-thalassemia minor) were analyzed at the Universidad Nacional de Tucumán, Argentina, between September 2013 and June 2014...
April 2017: Revista Brasileira de Hematologia e Hemoterapia
https://www.readbyqxmd.com/read/28575289/myod-and-foxo3-mediated-hotspot-interaction-orchestrates-super-enhancer-activity-during-myogenic-differentiation
#13
Xianlu L Peng, Karl K So, Liangqiang He, Yu Zhao, Jiajian Zhou, Yuying Li, Mingze Yao, Bo Xu, Suyang Zhang, Hongjie Yao, Ping Hu, Hao Sun, Huating Wang
Super-enhancers (SEs) are cis-regulatory elements enriching lineage specific key transcription factors (TFs) to form hotspots. A paucity of identification and functional dissection promoted us to investigate SEs during myoblast differentiation. ChIP-seq analysis of histone marks leads to the uncovering of SEs which remodel progressively during the course of differentiation. Further analyses of TF ChIP-seq enable the definition of SE hotspots co-bound by the master TF, MyoD and other TFs, among which we perform in-depth dissection for MyoD/FoxO3 interaction in driving the hotspots formation and SE activation...
June 1, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28570402/genetic-factors-involved-in-mandibular-prognathism
#14
Anna Doraczynska-Kowalik, Kamil H Nelke, Wojciech Pawlak, Maria M Sasiadek, Hanna Gerber
Mandibular prognathism is defined as an abnormal forward projection of the mandible beyond the standard relation to the cranial base and it is usually categorized as both a skeletal Class III pattern and Angle Class III malocclusion. The etiology of mandibular prognathism is still uncertain, with various genetic, epigenetic, and environmental factors possibly involved. However, many reports on its coexistence in both twins and segregation in families suggest the importance of genetic influences. A multifactorial and polygenic background with a threshold for expression or an autosomal dominant mode with incomplete penetrance and variable expressivity are the most probable inheritance patterns...
May 31, 2017: Journal of Craniofacial Surgery
https://www.readbyqxmd.com/read/28560380/sorafenib-induces-variations-of-the-dna-methylome-in-ha22t-vgh-human-hepatocellular-carcinoma-derived-cells
#15
Edoardo Abeni, Alessandro Salvi, Eleonora Marchina, Michele Traversa, Bruna Arici, Giuseppina De Petro
Sorafenib is currently used to treat advanced and/or unresectable hepatocellular carcinoma (HCC), but the increase of the median survival was only 3 months. Moreover, sorafenib has severe side effects and patients develop resistance quickly. Epigenetic alterations such as DNA methylation play a decisive role in the development and progression of HCC. To our knowledge, there are no studies that analysed the global DNA methylation changes in HCC cells treated with sorafenib. Using MeDip-chip technologies, we found 1230 differentially methylated genes in HA22T/VGH cells treated with sorafenib compared to untreated cells...
May 24, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28554751/correlations-of-foxo3-and-foxo4-expressions-with-clinicopathological-features-and-prognosis-of-bladder-cancer
#16
Yang Wang, Xin-Li Kang, Fan-Chang Zeng, Cong-Jie Xu, Jia-Quan Zhou, Dong-Ni Luo
OBJECTIVE: The study is performed to explore the correlations of forkhead box O3 (FoxO3) and forkhead box O4 (FoxO4) expressions with clinicopathological features and prognosis of bladder cancer. METHODS: Bladder cancer tissues and adjacent normal tissues from the recruited 222 patients were collected. Quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting and immunohistochemistry were applied to determine the expressions of FoxO3 and FoxO4...
April 20, 2017: Pathology, Research and Practice
https://www.readbyqxmd.com/read/28545464/c10orf10-depp-mediated-ros-accumulation-is-a-critical-modulator-of-foxo3-induced-autophagy
#17
S Salcher, M Hermann, U Kiechl-Kohlendorfer, M J Ausserlechner, P Obexer
BACKGROUND: Neuroblastoma is the most common solid tumor in childhood and develops from undifferentiated progenitor cells of the sympathetic nervous system. In neuronal tumor cells DNA-damaging chemotherapeutic agents activate the transcription factor FOXO3 which regulates the formation of reactive oxygen species (ROS) and cell death as well as a longevity program associated with therapy resistance. We demonstrated before that C10ORF10/DEPP, a transcriptional target of FOXO3, localizes to peroxisomes and mitochondria and impairs cellular ROS detoxification...
May 25, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28507102/foxo3-pgc-1%C3%AE-signaling-axis-is-essential-for-cancer-stem-cell-properties-of-pancreatic-ductal-adenocarcinoma
#18
Motofumi Kumazoe, Mika Takai, Shun Hiroi, Chieri Takeuchi, Mai Kadomatsu, Takashi Nojiri, Hiroaki Onda, Jaehoon Bae, Yuhui Huang, Kanako Takamatsu, Shuya Yamashita, Kenji Kangawa, Hirofumi Tachibana
In 95% of patients with pancreatic ductal adenocarcinoma (PDAC), recurrence is observed following chemotherapy. Findings from several studies have indicated that cancer stem cells (CSCs) are resistant to anti-cancer agents and may be involved in cancer recurrence and metastasis. The CD44 protein is a major CSC marker, and CD44 also plays an indispensable role in the CSC properties in several cancers, including pancreatic cancer; however, no clinical approach exists to inhibit CD44 activity. Here, we have performed knockin/knock down experiments and we demonstrate that the forkhead box O3 (FOXO3)/liver kinase B1 (LKB1)/AMP-activated protein kinase (AMPK)/PPAR-γ co-activator-1β (PGC- 1β)/pyruvate dehydrogenase -A1 (PDHA1) pathway is essential for CD44 expression and CSC properties...
May 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28465359/elevated-foxg1-and-sox2-in-glioblastoma-enforces-neural-stem-cell-identity-through-transcriptional-control-of-cell-cycle-and-epigenetic-regulators
#19
Harry Bulstrode, Ewan Johnstone, Maria Angeles Marques-Torrejon, Kirsty M Ferguson, Raul Bardini Bressan, Carla Blin, Vivien Grant, Sabine Gogolok, Ester Gangoso, Sladjana Gagrica, Christine Ender, Vassiliki Fotaki, Duncan Sproul, Paul Bertone, Steven M Pollard
Glioblastoma multiforme (GBM) is an aggressive brain tumor driven by cells with hallmarks of neural stem (NS) cells. GBM stem cells frequently express high levels of the transcription factors FOXG1 and SOX2. Here we show that increased expression of these factors restricts astrocyte differentiation and can trigger dedifferentiation to a proliferative NS cell state. Transcriptional targets include cell cycle and epigenetic regulators (e.g., Foxo3, Plk1, Mycn, Dnmt1, Dnmt3b, and Tet3). Foxo3 is a critical repressed downstream effector that is controlled via a conserved FOXG1/SOX2-bound cis-regulatory element...
April 15, 2017: Genes & Development
https://www.readbyqxmd.com/read/28445867/the-mir-106a-363xpcl1-mirna-cluster-induces-murine-t-cell-lymphoma-despite-transcriptional-activation-of-the-p27kip1-cell-cycle-inhibitor
#20
Daniel A Kuppers, Thomas M Schmitt, Harry C Hwang, Lavanya Samraj, Bruce E Clurman, Matthew L Fero
The miR-106a~363 cluster encodes 6 miRNAs on the X-chromosome which are abundant in blood cells and overexpressed in a variety of malignancies. The constituent miRNA of miR-106a~363 have functional activities in vitro that are predicted to be both oncogenic and tumor suppressive, yet little is known about their physiological functions in vivo. Mature miR-106a~363 (Mirc2) miRNAs are processed from an intragenic, non-protein encoding gene referred to as Xpcl1 (or Kis2), situated at an X-chromosomal locus frequently targeted by retroviruses in murine lymphomas...
April 7, 2017: Oncotarget
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