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https://www.readbyqxmd.com/read/28087474/foxo1-downregulation-is-associated-with-worse-outcome-in-bladder-cancer-and-adds-significant-prognostic-information-to-p53-overexpression
#1
Josep Lloreta, Alba Font-Tello, Núria Juanpere, Albert Frances, Marta Lorenzo, Lara Nonell, Silvia de Muga, Ivonne Vázquez, Lluís Cecchini, Silvia Hernández-Llodrà
Nuclear FOXOs mediate cell cycle arrest and promote apoptosis. FOXOs and p53 could have similar effects as tumor suppressor genes. In spite of extensive literature, little is known about the role of FOXO1 and its relationship with p53 status in bladder cancer. Expression of FOXO1 and p53 were analyzed by immunohistochemistry in 162 urothelial carcinomas (UC). Decreased FOXO1 expression, p53 overexpression and the combination FOXO1 downregulation/p53 overexpression were strongly associated with high grade (P=...
January 10, 2017: Human Pathology
https://www.readbyqxmd.com/read/28076456/propofol-inhibits-lung-cancer-cell-viability-and-induces-cell-apoptosis-by-upregulating-microrna-486-expression
#2
N Yang, Y Liang, P Yang, T Yang, L Jiang
Propofol is a frequently used intravenous anesthetic agent. Recent studies show that propofol exerts a number of non-anesthetic effects. The present study aimed to investigate the effects of propofol on lung cancer cell lines H1299 and H1792 and functional role of microRNA (miR)-486 in these effects. H1299 and/or H1792 cells were treated with or without propofol and transfected or not with miR-486 inhibitor, and then cell viability and apoptosis were analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and flow cytometry...
January 5, 2017: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://www.readbyqxmd.com/read/28069811/tgf-%C3%AE-1-smad3-pathway-targets-pp2a-ampk-foxo1-to-regulate-hepatic-gluconeogenesis
#3
Hariom Yadav, Samir Devalaraja, Stephanie Chung, Sushil G Rane
Maintenance of glucose homeostasis is essential for normal physiology. Deviation from normal glucose levels, in either direction, increases susceptibility to serious medical complications such as hypoglycemia or diabetes. Maintenance of glucose homeostasis is achieved via functional interactions amongst various organs, liver, skeletal muscle, adipose tissue, brain and the endocrine pancreas. The liver is the primary site for endogenous glucose production, especially during states of prolonged fasting. However, enhanced gluconeogenesis is also a signature feature of type 2 diabetes (T2D)...
January 9, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28064564/aspartate-inhibits-lps-induced-mafbx-and-murf1-expression-in-skeletal-muscle-in-weaned-pigs-by-regulating-akt-ampk%C3%AE-and-foxo1
#4
Yulan Liu, Xiuying Wang, Weibo Leng, Dingan Pi, Zhixiao Tu, Huiling Zhu, Haifeng Shi, Shuang Li, Yongqing Hou, Chien-An Andy Hu
Infection and inflammation can result in the rapid loss of muscle mass and myofibrillar proteins (muscle atrophy). In addition, aspartate (Asp) is necessary for protein synthesis in mammalian cells. We hypothesized that Asp could attenuate LPS-induced muscle atrophy in a piglet model. Twenty-four weaning piglets were allotted to four treatments, including non-challenged control, LPS challenged control, LPS+0.5% Asp and LPS+1.0% Asp. On d 21, the piglets were injected with i.p. injection of LPS (100 ug/kg BM) or saline...
January 2017: Innate Immunity
https://www.readbyqxmd.com/read/28058850/molecular-diagnostics-in-the-management-of-rhabdomyosarcoma
#5
Michael A Arnold, Fredric G Barr
A classification of rhabdomyosarcoma (RMS) with prognostic relevance has primarily relied on clinical features and histologic classification as either embryonal or alveolar RMS. The PAX3-FOXO1 and PAX7-FOXO1 gene fusions occur in 80% of cases with the alveolar subtype and are more predictive of outcome than histologic classification. Identifying additional molecular hallmarks that further subclassify RMS is an active area of research. Areas Covered: The authors review the current state of the PAX3-FOXO1 and PAX7-FOXO1 fusions as prognostic biomarkers...
January 6, 2017: Expert Review of Molecular Diagnostics
https://www.readbyqxmd.com/read/28057752/foxo1-inhibits-accelerated-%C3%AE-cell-aging-in-pancreas-specific-smad7-mutant-mice
#6
Xiangwei Xiao, Congde Chen, Ping Guo, Ting Zhang, Shane Fischbach, Joseph Carl Fusco, Chiyo Shiota, Krishna Prasadan, H Henry Dong, George K Gittes
The mechanisms underlying the effects of exocrine dysfunction on the development of diabetes remain largely unknown. Here, we show that pancreatic depletion of SMAD7 resulted in age-dependent increases in β-cell dysfunction, with accelerated glucose intolerance, followed by overt diabetes. The accelerated β-cell dysfunction and loss of proliferation capacity, two features of β-cell aging, appeared to be non-cell-autonomous, secondary to the adjacent exocrine failure as a bystander effect. Increased FoxO1 acetylation and nuclear retention was followed by progressive FoxO1 loss in β-cells, which marked the onset of diabetes...
January 5, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28055971/src-promotes-castration-recurrent-prostate-cancer-through-androgen-receptor-dependent-canonical-and-non-canonical-transcriptional-signatures
#7
Indranil Chattopadhyay, Jianmin Wang, Maochun Qin, Lingqiu Gao, Renae Holtz, Robert L Vessella, Robert W Leach, Irwin H Gelman
Progression of prostate cancer (PC) to castration-recurrent growth (CRPC) remains dependent on sustained expression and transcriptional activity of the androgen receptor (AR). A major mechanism contributing to CRPC progression is through the direct phosphorylation and activation of AR by Src-family (SFK) and ACK1 tyrosine kinases. However, the AR-dependent transcriptional networks activated by Src during CRPC progression have not been elucidated. Here, we show that activated Src (Src527F) induces androgen-independent growth in human LNCaP cells, concomitant with its ability to induce proliferation/survival genes normally induced by dihydrotestosterone (DHT) in androgen-dependent LNCaP and VCaP cells...
December 31, 2016: Oncotarget
https://www.readbyqxmd.com/read/28052003/mir-138-5p-suppresses-autophagy-in-pancreatic-cancer-by-targeting-sirt1
#8
She Tian, Xingjun Guo, Chao Yu, Chengyi Sun, Jianxin Jiang
The role of microRNA in the aberrant autophagy that occurs in pancreatic cancer remains controversial. Because hypoxia is known to induce autophagy, we screened for differentially expressed microRNAs using a miRNA microarray with pancreatic cancer cells cultured under normoxic and hypoxic conditions. We found that miR-138-5p was among the most downregulated miRNA in hypoxia-stimulated cells, and that overexpression of miR-138-5p substantially reduced expression of autophagy markers. In addition, western blot and immunofluorescence analyses and electron microscopy revealed that miR-138-5p inhibited autophagy in pancreatic cancer cells and blocked serum starvation-induced autophagic flux independently of the typical autophagic signaling pathway...
December 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/28049237/the-foxo1-gene-obesity-interaction-increases-the-risk-of-type-2-diabetes-mellitus-in-a-chinese-han-population
#9
Lilin Gong, Rong Li, Wei Ren, Zengchan Wang, Zhihong Wang, Maosheng Yang, Suhua Zhang
Here, we aimed to study the effect of the forkhead box O1-insulin receptor substrate 2 (FOXO1-IRS2) gene interaction and the FOXO1 and IRS2 genes-environment interaction for the risk of type 2 diabetes mellitus (T2DM) in a Chinese Han population. We genotyped 7 polymorphism sites of FOXO1 gene and IRS2 gene in 780 unrelated Chinese Han people (474 cases of T2DM, 306 cases of healthy control). The risk of T2DM in individuals with AA genotype for rs7986407 and CC genotype for rs4581585 in FOXO1 gene was 2.092 and 2...
February 2017: Journal of Korean Medical Science
https://www.readbyqxmd.com/read/28043741/exposure-to-benzo-a-pyrene-impairs-decidualization-and-decidual-angiogenesis-in-mice-during-early-pregnancy
#10
Xueyan Li, Cha Shen, Xueqing Liu, Junlin He, Yubin Ding, Rufei Gao, Xinyi Mu, Yanqing Geng, Yingxiong Wang, Xuemei Chen
Benzo[a]pyrene (BaP) is a ubiquitous environmental persistent organic pollutant and a well-known endocrine disruptor. BaP exposure could alter the steroid balance in females. Endometrium decidualization and decidual angiogenesis are critical events for embryo implantation and pregnancy maintenance during early pregnancy and are modulated by steroids. However, the effect of BaP on decidualization is not clear. This study aimed to explore the effects of BaP on decidualization and decidual angiogenesis in pregnant mice...
December 30, 2016: Environmental Pollution
https://www.readbyqxmd.com/read/28039360/inhibition-of-ubc13-mediated-ubiquitination-by-gps2-regulates-multiple-stages-of-b-cell-development
#11
Claudia Lentucci, Anna Belkina, Carly T Cederquist, Michelle Chan, Holly E Johnson, Sherry Prasad, Amanda Lopacinski, Barbara S Nikolajczyk, Stefano Monti, Jennifer Snyder-Cappione, Bogdan Tanasa, Maria Dafne Cardamone, Valentina Perissi
Non-proteolytic ubiquitin signaling mediated by K63 ubiquitin chains plays a critical role in multiple pathways that are key to the development and activation of immune cells. Our previous work indicates that G-Protein Suppressor 2 (GPS2) is a multi-functional protein regulating TNFα signaling and lipid metabolism in the adipose tissue through modulation of K63 ubiquitination events. However, the full extent of GPS2-mediated regulation of ubiquitination and the underlying molecular mechanisms are unknown. Here, we report that GPS2 is required for restricting the activation of TLR and BCR signaling pathways and the AKT/FOXO1 pathway in immune cells based on direct inhibition of Ubc13 enzymatic activity...
December 30, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28035744/impact-of-fusion-gene-status-versus-histology-on-risk-stratification-for-rhabdomyosarcoma-retrospective-analyses-of-patients-on-uk-trials
#12
Joanna Selfe, David Olmos, Reem Al-Saadi, Khin Thway, Julia Chisholm, Anna Kelsey, Janet Shipley
BACKGROUND: Long-term toxicities from current treatments are a major issue in paediatric cancer. Previous studies, including our own, have shown prognostic value for the presence of PAX3/7-FOXO1 fusion genes in rhabdomyosarcoma (RMS). It is proposed to introduce PAX3/7-FOXO1 positivity as a component of risk stratification, rather than alveolar histology, in future clinical trials. PROCEDURE: To assess the potential impact of this reclassification, we have determined the changes to risk category assignment of 210 histologically reviewed patients treated in the UK from previous malignant mesenchymal tumour clinical trials for non-metastatic RMS based on identification of PAX3/7-FOXO1 by fluorescence in situ hybridisation and/or reverse transcription PCR...
December 30, 2016: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28035217/the-possible-role-of-diet-in-the-pathogenesis-of-adult-female-acne
#13
REVIEW
Krystyna Romańska-Gocka, Magdalena Woźniak, Elżbieta Kaczmarek-Skamira, Barbara Zegarska
Acne in adults is a chronic, increasingly common disease, especially among women. It differs in pathogenesis and clinical presentation from adolescent acne. Acne in adults is associated with Western diet, defined as high consumption of milk, high glycemic load and high calorie intake. Metabolic signals of this diet result in a significant increase in insulin/insulin growth factor 1 serum level and consequently in the molecular interplay of mammalian target of rapamycin complex 1 kinase (mTORC1)/forkhead box protein 1 (FoxO1) mediated nutrient signaling, leading to increased proliferation of keratinocytes, increased lipogenesis and sebum production and finally to aggravation of acne...
December 2016: Postȩpy Dermatologii i Alergologii
https://www.readbyqxmd.com/read/28031476/5-hydroxytryptamine-synthesized-in-the-aorta-gonad-mesonephros-regulates-hematopoietic-stem-and-progenitor-cell-survival
#14
Junhua Lv, Lu Wang, Ya Gao, Yu-Qiang Ding, Feng Liu
The in vitro or ex vivo production of transplantable hematopoietic stem cells (HSCs) holds great promise for the treatment of hematological diseases in the clinic. However, HSCs have not been produced from either embryonic or induced pluripotent stem cells. In this study, we report that 5-hydroxytryptamine (5-HT; also called serotonin) can enhance the generation of hematopoietic stem and progenitor cells (HSPCs) in vitro and is essential for the survival of HSPCs in vivo during embryogenesis. In tryptophan hydroxylase 2-deficient embryos, a decrease in 5-HT synthesized in the aorta-gonad-mesonephros leads to apoptosis of nascent HSPCs...
December 28, 2016: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28024794/does-resveratrol-improve-insulin-signalling-in-hepg2-cells
#15
Marjan Norouzzadeh, Fatemehsadat Amiri, Ali Akbar Saboor-Yaraghi, Farnoosh Shemirani, Yas Kalikias, Loghman Sharifi, Monireh Sadat Seyyedsalehi, Maryam Mahmoudi
OBJECTIVES: Diabetes mellitus is a common metabolic disorder with high global prevalence. It is characterized by a decrease in insulin secretion or a decrease in insulin sensitivity or both. The aim of the present study was to investigate the effects of resveratrol treatment on the expression of the genes involved in insulin signalling cascade, such as Forkhead box protein O1 (FoxO1), 3-phosphoinositide-dependent protein kinase 1 (PDPK1) and mammalian target of rapamycin (mTOR). METHODS: HepG2 cells were cultured in serum-free medium with high concentrations of glucose and insulin and then were treated with resveratrol (5, 10 and 20 µM) for 24 and 48 hours...
December 23, 2016: Canadian Journal of Diabetes
https://www.readbyqxmd.com/read/28011637/tribbles-pseudokinase-3-induces-both-apoptosis-and-autophagy-in-amyloid-%C3%AE-induced-neuronal-death
#16
Suraiya Saleem, Subhas Chandra Biswas
Amyloid-β (Aβ) induced neuron death is considered central to the pathogenesis of Alzheimer disease (AD). Among several death modalities, autophagy and apoptosis play important roles in Aβ-induced neuron death suggesting that there may be regulatory mechanisms that initiate both cell death pathways. However, molecules that govern both pathways have not been identified. Here, we report that, upon Aβ treatment, tribbles pseudokinase 3 (TRIB3, an ortholog of Drosophila Tribbles), is upregulated in neurons, both in vivo and in vitro...
December 23, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28009298/adenovirus-protein-e4-orf1-activation-of-pi3-kinase-reveals-differential-regulation-of-downstream-effector-pathways-in-adipocytes
#17
Natasha Chaudhary, Eva Gonzalez, Sung-Hee Chang, Fuqiang Geng, Shahin Rafii, Nasser K Altorki, Timothy E McGraw
Insulin activation of phosphatidylinositol 3-kinase (PI3K) regulates metabolism, including the translocation of the Glut4 glucose transporter to the plasma membrane and inactivation of the FoxO1 transcription factor. Adenoviral protein E4-ORF1 stimulates cellular glucose metabolism by mimicking growth-factor activation of PI3K. We have used E4-ORF1 as a tool to dissect PI3K-mediated signaling in adipocytes. E4-ORF1 activation of PI3K in adipocytes recapitulates insulin regulation of FoxO1 but not regulation of Glut4...
December 20, 2016: Cell Reports
https://www.readbyqxmd.com/read/28009285/anabolism-associated-mitochondrial-stasis-driving-lymphocyte-differentiation-over-self-renewal
#18
William C Adams, Yen-Hua Chen, Radomir Kratchmarov, Bonnie Yen, Simone A Nish, Wen-Hsuan W Lin, Nyanza J Rothman, Larry L Luchsinger, Ulf Klein, Meinrad Busslinger, Jeffrey C Rathmell, Hans-Willem Snoeck, Steven L Reiner
Regeneration requires related cells to diverge in fate. We show that activated lymphocytes yield sibling cells with unequal elimination of aged mitochondria. Disparate mitochondrial clearance impacts cell fate and reflects larger constellations of opposing metabolic states. Differentiation driven by an anabolic constellation of PI3K/mTOR activation, aerobic glycolysis, inhibited autophagy, mitochondrial stasis, and ROS production is balanced with self-renewal maintained by a catabolic constellation of AMPK activation, mitochondrial elimination, oxidative metabolism, and maintenance of FoxO1 activity...
December 20, 2016: Cell Reports
https://www.readbyqxmd.com/read/28007970/dual-effects-of-fructose-on-chrebp-and-foxo1-3%C3%AE-are-responsible-for-aldob-upregulation-and-vascular-remodeling
#19
Wei Cao, Tuanjie Chang, Xiao-Qiang Li, Rui Wang, Lingyun Wu
Increased production of methylglyoxal (MG) in vascular tissues is one of the causative factors for vascular remodeling in different subtypes of metabolic syndrome, including hypertension and insulin resistance. Fructose-induced upregulation of aldolase B (AldoB) contributes to increased vascular MG production but the underlying mechanisms have been unclear. Serum levels of MG and fructose were determined in diabetic patients with hypertension. MG level had significant positive correlations with blood pressure and fructose level respectively...
December 22, 2016: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28007786/myc-mycn-mediated-glycolysis-enhances-mouse-spermatogonial-stem-cell-self-renewal
#20
Mito Kanatsu-Shinohara, Takashi Tanaka, Narumi Ogonuki, Atsuo Ogura, Hiroko Morimoto, Pei Feng Cheng, Robert N Eisenman, Andreas Trumpp, Takashi Shinohara
Myc plays critical roles in the self-renewal division of various stem cell types. In spermatogonial stem cells (SSCs), Myc controls SSC fate decisions because Myc overexpression induces enhanced self-renewal division, while depletion of Max, a Myc-binding partner, leads to meiotic induction. However, the mechanism by which Myc acts on SSC fate is unclear. Here we demonstrate a critical link between Myc/Mycn gene activity and glycolysis in SSC self-renewal. In SSCs, Myc/Mycn are regulated by Foxo1, whose deficiency impairs SSC self-renewal...
December 1, 2016: Genes & Development
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