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https://www.readbyqxmd.com/read/29141605/an-intronic-single-nucleotide-polymorphism-rs13217795-in-foxo3-is-associated-with-asthma-and-allergic-rhinitis-a-case-case-control-study
#1
Justin Z Amarin, Randa G Naffa, Haya H Suradi, Yousof M Alsaket, Nathir M Obeidat, Tareq M Mahafza, Malek A Zihlif
BACKGROUND: Asthma and allergic rhinitis are respiratory diseases with a significant global burden. Forkhead box O3 (FOXO3) is a gene involved in the etiology of a number of respiratory diseases. The objective of this study is to assess the association of rs13217795, an intronic FOXO3 single-nucleotide polymorphism, with asthma and allergic rhinitis. METHODS: In this case-case-control genetic association study, genotyping was conducted using the PCR-RFLP method...
November 15, 2017: BMC Medical Genetics
https://www.readbyqxmd.com/read/29137289/lingguizhugan-decoction-improves-non-alcoholic-fatty-liver-disease-by-altering-insulin-resistance-and-lipid-metabolism-related-genes-a-whole-trancriptome-study-by-rna-seq
#2
Mingzhe Zhu, Shijun Hao, Tao Liu, Lili Yang, Peiyong Zheng, Li Zhang, Guang Ji
Lingguizhugan decoction, a classic traditional Chinese medicine formula, has been used to treat non-alcoholic fatty liver disease (NAFLD), however, the underlying mechanisms remains unclear. In the present study, we compared the phenotype of the normal rats (fed with chow diet), high-fat-diet (HFD) induced NAFLD rats and Lingguizhugan decoction (LGZG, comprises four Chinese herbs: Poria, Ramulus Cinnamomi, Rhizoma Atractylodis Macrocephalae, and Radix Glycyrrhizae.) intervened rats, and detected whole genome gene expression by RNA-Seq...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29136250/genetic-overlap-between-schizophrenia-and-volumes-of-hippocampus-putamen-and-intracranial-volume-indicates-shared-molecular-genetic-mechanisms
#3
Olav B Smeland, Yunpeng Wang, Oleksandr Frei, Wen Li, Derrek P Hibar, Barbara Franke, Francesco Bettella, Aree Witoelar, Srdjan Djurovic, Chi-Hua Chen, Paul M Thompson, Anders M Dale, Ole A Andreassen
Schizophrenia (SCZ) is associated with differences in subcortical brain volumes and intracranial volume (ICV). However, little is known about the underlying etiology of these brain alterations. Here, we explored whether brain structure volumes and SCZ share genetic risk factors. Using conditional false discovery rate (FDR) analysis, we integrated genome-wide association study (GWAS) data on SCZ (n = 82315) and GWAS data on 7 subcortical brain volumes and ICV (n = 11840). By conditioning the FDR on overlapping associations, this statistical approach increases power to discover genetic loci...
November 9, 2017: Schizophrenia Bulletin
https://www.readbyqxmd.com/read/29136142/the-forkhead-transcription-factor-foxo3-negatively-regulates-natural-killer-cell-function-and-viral-clearance-in-myocarditis
#4
Madlen Loebel, Luise Holzhauser, Jelka A Hartwig, Praphulla C Shukla, Konstantinos Savvatis, Alexander Jenke, Martina Gast, Felicitas Escher, Sonya C Becker, Sandra Bauer, Andrea Stroux, Antje Beling, Meike Kespohl, Sandra Pinkert, Henry Fechner, Uwe Kuehl, Dirk Lassner, Wolfgang Poller, Heinz-Peter Schultheiss, Tanja Zeller, Stefan Blankenberg, Anna-Pia Papageorgiou, Stephane Heymans, Ulf Landmesser, Carmen Scheibenbogen, Carsten Skurk
Aims: Foxo3 is a transcription factor involved in cell metabolism, survival, and inflammatory disease. However, mechanistic insight in Foxo3 effects is still limited. Here, we investigated the role of Foxo3 on natural killer (NK) cell responses and its effects in viral myocarditis. Methods and results: Effects of Foxo3 on viral load and immune responses were investigated in a model of coxsackie virus B3 myocarditis in wild-type (WT) and Foxo3 deficient mice. Reduced immune cell infiltration, viral titres, and pro-inflammatory cytokines in cardiac tissue were observed in Foxo3-/- mice 7 days post-infection (p...
November 9, 2017: European Heart Journal
https://www.readbyqxmd.com/read/29099866/investigation-of-foxo3-dynamics-during-erythroblast-development-in-%C3%AE-thalassemia-major
#5
Naruchit Thanuthanakhun, Lalana Nuntakarn, Somponnat Sampattavanich, Usanarat Anurathapan, Suphanun Phuphanitcharoenkun, Savichaya Pornpaiboonstid, Suparerk Borwornpinyo, Suradej Hongeng
The FoxO3 transcription factor is a key regulator of oxidative stress and erythroid maturation during erythropoiesis. In this study, we explored the involvement of FoxO3 in severe β-thalassemia. Using primary CD34+ hematopoietic progenitor cells from patients with β-thalassemia major, we successfully developed an in vitro model of ineffective erythropoiesis. Based on this model, FoxO3 activity was quantified in single cells using high throughput imaging flow cytometry. This study revealed a significant reduction of FoxO3 activity during the late stage of erythroblast differentiation in β-thalassemia, in contrast to erythropoiesis in normal cells that maintain persistent activation of FoxO3...
2017: PloS One
https://www.readbyqxmd.com/read/29080996/impact-of-local-heating-and-cooling-on-skeletal-muscle-transcriptional-response-related-to-myogenesis-and-proteolysis
#6
Roksana B Zak, B M Hassenstab, L K Zuehlke, M W S Heesch, R J Shute, T L Laursen, D T LaSalle, D R Slivka
PURPOSE: To determine the impact of local muscle heating and cooling on myogenic and proteolytic gene responses following resistance exercise. METHODS: Recreationally trained males (n = 12), age 25.3 ± 1.5, % body fat 13.6 ± 1.92, completed four sets of 8-12 repetitions of unilateral leg press and leg extension while heating one leg, and cooling the other. Muscle biopsies were taken from the vastus lateralis of each leg pre and 4 h post exercise. RESULTS: MyoD, FOXO1, and MuRF1 mRNA increased with exercise regardless of temperature (p < 0...
October 28, 2017: European Journal of Applied Physiology
https://www.readbyqxmd.com/read/29072689/mir-629-promotes-human-pancreatic-cancer-progression-by-targeting-foxo3
#7
Haijiao Yan, Qing Li, Jun Wu, Wenwei Hu, Jingting Jiang, Liangrong Shi, Xin Yang, Danxia Zhu, Mei Ji, Changping Wu
The FOXO signaling pathway has been reported to have an important role in human cancer. Expression of miR-629 was markedly upregulated in pancreatic cancer and negatively correlated with FOXO3. Therefore, exploring the regulatory mechanism of miR-629 and FOXO3 signaling may provide valuable clinical targets for pancreatic cancer therapy. In the current study, we found that overexpressing and inhibiting miR-629, respectively, enhanced and reduced the cell proliferation and metastasis of pancreatic cancer cells in vitro and in vivo compared with parental cells or cells transfected with a control vector...
October 26, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29058455/newborn-neurons-are-damaged-in-vitro-by-a-low-concentration-of-silver-nanoparticles-through-the-inflammatory-oxidative-stress-pathway
#8
Xiaoyuan Guo, Guilong Zhang, Lukui Chen, Ahsan Ali Khan, Bin Gu, Bingqian Li
With increasing applications of nanomaterials, including silver nanoparticles (AgNPs), unknown potential risks are present against humans and the environment, especially to the fetus and neonates, which are more sensitive to the cytotoxicity of such agents. This study focused on the effects of AgNP exposure on newborn neurons differentiated from neural stem cells (NSCs) in vitro. We isolated NSCs from fetal rat hippocampus and incubated them in neural differentiation medium for 3-7 days to form newborn neurons and networks...
October 23, 2017: DNA and Cell Biology
https://www.readbyqxmd.com/read/29057166/regulation-of-exercise-induced-autophagy-in-skeletal-muscle
#9
Altea Rocchi, Congcong He
PURPOSE OF REVIEW: Physical exercise is a highly effective method to prevent several pathogenic conditions, such as obesity, type 2 diabetes and cardiovascular diseases, largely due to metabolic adaptations induced by exercise in skeletal muscle. Yet how exercise induces the beneficial effects in muscle remains to be fully elucidated. Autophagy is a lysosomal degradation pathway that regulates nutrient recycling, energy production and organelle quality control. The autophagy pathway is upregulated in response to stress during exercise and muscle contraction, and may be an important mechanism mediating exercise-induced health benefits...
June 2017: Current Pathobiology Reports
https://www.readbyqxmd.com/read/29049183/identifying-key-genes-associated-with-acute-myocardial-infarction
#10
Ming Cheng, Shoukuan An, Junquan Li
BACKGROUND: This study aimed to identify key genes associated with acute myocardial infarction (AMI) by reanalyzing microarray data. METHODS: Three gene expression profile datasets GSE66360, GSE34198, and GSE48060 were downloaded from GEO database. After data preprocessing, genes without heterogeneity across different platforms were subjected to differential expression analysis between the AMI group and the control group using metaDE package. P < .05 was used as the cutoff for a differentially expressed gene (DEG)...
October 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28986382/loss-of-foxo1-cooperates-with-tmprss2-erg-overexpression-to-promote-prostate-tumorigenesis-and-cell-invasion
#11
Yinhui Yang, Alexandra M Blee, Dejie Wang, Jian An, Yunqian Pan, Yuqian Yan, Tao Ma, Yundong He, Joseph Dugdale, Xiaonan Hou, Jun Zhang, S John Weroha, Wei-Guo Zhu, Y Alan Wang, Ronald A DePinho, Wanhai Xu, Haojie Huang
E26 transformation-specific (ETS) transcription factor ERG is aberrantly overexpressed in approximately 50% of all human PCa due to TMPRSS2-ERG gene rearrangements. However, mice with prostate-specific transgenic expression of PCa-associated ERG alone fail to develop PCa, highlighting that ERG requires other lesions to drive prostate tumorigenesis. Forkhead box (FOXO) transcription factor FOXO1 is a tumor suppressor that is frequently inactivated in human PCa. Here we demonstrate that FOXO1, but not other FOXO proteins (FOXO3 and FOXO4), binds and inhibits the transcriptional activity of PCa-associated ERG independently of FOXO1 transcriptional activity...
October 6, 2017: Cancer Research
https://www.readbyqxmd.com/read/28979810/enhancing-chemotherapy-sensitivity-by-targeting-pcg-via-the-atm-p53-pathway
#12
Shu-Bin Gao, Kang-Li Li, Huan Qiu, Ling-Yu Zhu, Chang-Bao Pan, Yue Zhao, Shu-Hua Wei, Shu Shi, Guang-Hui Jin, Li-Xiang Xue
Histone modification and chromatin remodeling are important events in response to DNA damage, and Polycomb group (PcG) proteins, catalyzing H3K27 methylation, are involved. However, the biological function and mechanism of PcG in DNA damage are not fully understood. Additionally, downstream effectors in hepatocellular carcinoma (HCC) remain unclear. The present study investigated the biological and mechanistic roles of PcG in the DNA damage response induced by chemotherapeutic drugs in HCC. It was found that chemotherapy drugs, such as epirubicin (EPB) and mitomycin C (MMC), effectively blocked expression of PcG in p53-wild-type HepG2 cells but not in PLC/PRF5 and Hep3B cells with p53 mutation or deletion...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/28977569/effects-of-foxo3-polymorphisms-on-survival-to-extreme-longevity-in-four-centenarian-studies
#13
Harold Bae, Anastasia Gurinovich, Alberto Malovini, Gil Atzmon, Stacy L Andersen, Francesco Villa, Nir Barzilai, Annibale Puca, Thomas T Perls, Paola Sebastiani
Previous studies note specific FOXO3 single-nucleotide polymorphisms (SNPs) associated with human longevity. However, it is not clear if these SNPs influence mortality risk beyond the oldest 1 percentile of survival. Using data from four longevity studies (total n = 8,266, age range 96-119 years for cases), we tested gene-wide association between 107 SNPs and survival to at least the oldest 1 percentile of survival for the 1900 birth cohort (≥96, white males; ≥100 white females). This analysis replicated 17 previously published variants, several of which are significant expression quantitative trait loci of FOXO3; rs6911407 and rs2253310 have the most significant effect on FOXO3 expressions in brain tissue...
July 18, 2017: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/28952285/hepatic-insulin-like-growth-factor-receptor-is-upregulated-by-activation-of-the-gsk3b-foxo3-pathway-after-partial-hepatectomy
#14
C Y E, Y Cai, B Z Sun, L Y Guan, T Jiang
Liver regeneration after partial hepatectomy (PH) is a complex and well-elaborated biological process whereby synchronized cell proliferation is induced in response to the loss of liver mass. Insulin-like growth factor 1 (IGF1) signaling, which plays a crucial role in normal growth and development, is involved in the process of liver regeneration. To assess the changes in the levels of serum IGF1 and hepatic IGF1 receptor (IGF1R), we established a mouse model for PH. This also allowed us to further explore the mechanisms that participate in the regulation of liver regeneration...
July 2017: Journal of Biological Regulators and Homeostatic Agents
https://www.readbyqxmd.com/read/28943389/single-step-genome-wide-association-studies-based-on-genotyping-by-sequence-data-reveals-novel-loci-for-the-litter-traits-of-domestic-pigs
#15
Pingxian Wu, Qiang Yang, Kai Wang, Jie Zhou, Jideng Ma, Qianzhi Tang, Long Jin, Weihang Xiao, Anan Jiang, Yanzhi Jiang, Li Zhu, Xuewei Li, Guoqing Tang
In this study, data genotyping by sequence (GBS) was used to perform single step GWAS (ssGWAS) to identify SNPs associated with the litter traits in domestic pigs and search for candidate genes in the region of significant SNPs. After quality control, 167,355 high-quality SNPs from 532 pigs were obtained. Phenotypic traits on 2112 gilt litters from 532 pigs were recorded including total number born (TNB), number born alive (NBA), and litter weight born alive (LWB). A single-step genomic BLUP approach (ssGBLUP) was used to implement the genome-wide association analysis at a 5% genome-wide significance level...
September 21, 2017: Genomics
https://www.readbyqxmd.com/read/28938528/p53-independent-p21-induction-by-melk-inhibition
#16
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...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28927457/p53-key-conductor-of-all-anti-acne-therapies
#17
REVIEW
Bodo C Melnik
This review based on translational research predicts that the transcription factor p53 is the key effector of all anti-acne therapies. All-trans retinoic acid (ATRA) and isotretinoin (13-cis retinoic acid) enhance p53 expression. Tetracyclines and macrolides via inhibiting p450 enzymes attenuate ATRA degradation, thereby increase p53. Benzoyl peroxide and hydrogen peroxide elicit oxidative stress, which upregulates p53. Azelaic acid leads to mitochondrial damage associated with increased release of reactive oxygen species inducing p53...
September 19, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28924380/intracellular-insulin-and-impaired-autophagy-in-a-zebrafish-model-and-a-cell-model-of-type-2-diabetes
#18
Xiang-Hui Meng, Bo Chen, Jing-Pu Zhang
Type 2 diabetes mellitus is characterized by insulin resistance. However, the complete molecular mechanism remains unclear. In this study, zebrafish were fed a long-term high-fat diet to induce type 2 diabetes, which resulted in a higher body weight, body mass index, more lipid vacuoles in liver, increased insulin transcription level in liver, brain and muscle, and high fasting blood glucose in the high-fat diet zebrafish. Oppositely, the transcription levels of insulin substrate-2 and glucose transporter 2 were significantly decreased, indicating insulin signaling pathway and glucose transport impaired in the insulin-targeting tissues...
2017: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/28905195/experimental-evidences-for-mir-30b-as-a-negative-regulator-of-foxo3-upregulated-by-kynurenine
#19
Zhi-Qing Duan, Yan Li, Lu Li
Molecular constituents regulated by the microenvironment components profoundly influence the propensity of cancer metastasis, a key event of estimating therapeutic actions of anticancer drugs. On one hand, kynurenine (Kyn), one of the microenvironment components, plays key roles in the metastasis of cancer cells in vivo; on the other hand, forkhead box O3 (FOXO3) can serve as a therapeutic target of various anticancer drugs. However, the effect of Kyn on FOXO3 is still not clear. The current study demonstrated that the selected dose of Kyn significantly upregulated the FOXO3 protein rather than FOXO3 messenger RNA (mRNA) in the lung cancer 95D cells...
September 13, 2017: Immunologic Research
https://www.readbyqxmd.com/read/28894507/foxo-transcriptional-factors-and-long-term-living
#20
REVIEW
Ghulam Murtaza, Abida Kalsoom Khan, Rehana Rashid, Saiqa Muneer, Syed Muhammad Farid Hasan, Jianxin Chen
Several pathologies such as neurodegeneration and cancer are associated with aging, which is affected by many genetic and environmental factors. Healthy aging conceives human longevity, possibly due to carrying the defensive genes. For instance, FOXO (forkhead box O) genes determine human longevity. FOXO transcription factors are involved in the regulation of longevity phenomenon via insulin and insulin-like growth factor signaling. Only one FOXO gene (FOXO DAF-16) exists in invertebrates, while four FOXO genes, that is, FOXO1, FOXO3, FOXO4, and FOXO6 are found in mammals...
2017: Oxidative Medicine and Cellular Longevity
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