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FoxO1

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https://www.readbyqxmd.com/read/29238041/foxo1-is-a-regulator-of-mhc-ii-expression-and-anti-tumor-effect-of-tumor-associated-macrophages
#1
Jing-Bo Yang, Zhi-Bin Zhao, Qing-Zhi Liu, Tai-Dou Hu, Jie Long, Kai Yan, Zhe-Xiong Lian
Macrophages are a critical component in host immune responses against tumor. In this work we investigated the role of forkhead box O1 (FoxO1) in the transcriptional regulation in macrophages, which affects the anti-tumor functions of tumor-associated macrophages (TAMs). First, we showed that TAMs expressed reduced levels of FoxO1, which was associated with their protumoral M2 polarization state. The suppression of FoxO1 expression in TAM was induced by the hypoxic condition in the tumor microenviroment. Next, we confirmed that FoxO1 positively regulates MHC-II genes by binding to the promoter region of Ciita gene, the master activator of multiple MHC-II genes...
December 14, 2017: Oncogene
https://www.readbyqxmd.com/read/29233846/ve-cadherin-mediated-epigenetic-regulation-of-endothelial-gene-expression
#2
Marco F Morini, Costanza Giampietro, Monica Corada, Federica Pisati, Elisa Lavarone, Sara I Cunha, Lei L Conze, Nicola J O'Reilly, Dhira Joshi, Svend Kjaer, Roger George, Emma Nye, Anqi Ma, Jian Jin, Richard Mitter, Michela Lupia, Ugo Cavallaro, Diego Pasini, Dinis P Calado, Elisabetta Dejana, Andrea Taddei
Rationale: The mechanistic foundation of vascular maturation is still largely unknown. Several human pathologies are characterized by deregulated angiogenesis and unstable blood vessels. Solid tumours, for instance, get their nourishment from newly formed structurally abnormal vessels which present wide and irregular inter-endothelial junctions. Expression and clustering of the main endothelial-specific adherens junction protein, vascular endothelial (VE)-cadherin (VEC), upregulate genes with key roles in endothelial differentiation and stability...
December 12, 2017: Circulation Research
https://www.readbyqxmd.com/read/29233659/klotho-upregulation-contributes-to-the-neuroprotection-of-ligustilide-against-cerebral-ischemic-injury-in-mice
#3
Fang-Yi Long, Men-Qi Shi, Hong-Jing Zhou, Dong-Ling Liu, Na Sang, Jun-Rong Du
Klotho, an aging-suppressor gene, encodes a protein that potentially acts as a neuroprotective factor. Our previous studies showed that ligustilide minimizes the cognitive dysfunction and brain damage induced by cerebral ischemia; however, the underlying mechanisms remain unclear. This study aims to investigate whether klotho is involved in the protective effects of ligustilide against cerebral ischemic injury in mice. Cerebral ischemia was induced by bilateral common carotid arterial occlusion. Neurobehavioral tests as well as Nissl and Fluoro-Jade B staining were used to evaluate the protective effects of ligustilide in cerebral ischemia, and Western blotting and ELISA approaches were used to investigate the underlying mechanisms...
December 9, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29227245/clearance-of-senescent-decidual-cells-by-uterine-natural-killer-cells-in-cycling-human-endometrium
#4
Paul J Brighton, Yojiro Maruyama, Katherine Fishwick, Pavle Vrljicak, Shreeya Tewary, Risa Fujihara, Joanne Muter, Emma S Lucas, Taihei Yamada, Laura Woods, Raffaella Lucciola, Yie Hou Lee, Satoru Takeda, Sascha Ott, Myriam Hemberger, Siobhan Quenby, Jan Joris Brosens
In cycling human endometrium, menstruation is followed by rapid estrogen-dependent growth. Upon ovulation, progesterone and rising cellular cAMP levels activate the transcription factor Forkhead box O1 (FOXO1) in endometrial stromal cells (EnSCs), leading to cell cycle exit and differentiation into decidual cells that control embryo implantation. Here we show that FOXO1 also causes acute senescence of a subpopulation of decidualizing EnSCs in an IL-8 dependent manner. Selective depletion or enrichment of this subpopulation revealed that decidual senescence drives the transient inflammatory response associated with endometrial receptivity...
December 11, 2017: ELife
https://www.readbyqxmd.com/read/29226969/cudratricusxanthone-a-attenuates-sepsis-induced-liver-injury-via-sirt1-signaling
#5
Yuri Lee, Gil-Saeng Jeong, Wonhwa Lee, Jong-Sup Bae
Cudratricusxanthone A (CTXA), a natural bioactive compound extracted from the roots of Cudraniatricuspidata Bureau, is known to possess antithrombotic, antiproliferative and antiinflammatory activities. It remains unclear that CTXA can improve hepatoprotective activity in vivo. The objective of this study was to investigate the effect of CTXA on lipopolysaccharide (LPS)-induced liver failure in mice, and to elucidate its underlying molecular mechanisms. Liver failure was induced by LPS (15 mg/kg, i.p.) in mice, and 12 h later, they were treated intravenously with CTXA...
December 11, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29224910/regulation-of-sirt3-foxo1-signaling-pathway-in-rats-with-non-alcoholic-steatohepatitis-by-salvianolic-acid-b
#6
Yingchun Wang, Juan Chen, Weizong Kong, Ruiping Zhu, Kai Liang, Quanxiang Kan, Yanhong Lou, Xiangyu Liu
AIMS: To explore the effect of salvianolic acid B (Sal B) on regulation of SIRT3/FOXO1 signaling pathway in rats with non-alcoholic steatohepatitis (NASH). METHODS: Sixty Sprague Dawley (SD) rats were randomly divided into control, model and treatment groups. After 12 weeks of successful model establishment with high fat diet, treatment group was given Sal B by intragastric administration. After 12 weeks of treatment, rats were sacrificed and livers were taken to test indicators such as liver index, TG, TC, ALT, AST, reactive oxygen species (ROS) by DCFH-DA probe, SOD2 activity by WST-8 test...
December 7, 2017: Archives of Medical Research
https://www.readbyqxmd.com/read/29224278/-clinicopathologic-and-molecular-genetic-characterizations-of-biphenotypic-sinonasal-sarcoma
#7
M Zhao, Q Y LaoI, D H Zhao, J Ma, G Q Ru, X L He, Z Wang, J Wang
Objective: To investigate the clinicopathologic characteristics, immunophenotypes, molecular genetics, and diagnostic and differential diagnostic features of biphenotypic sinonasal sarcoma (BSNS). Methods: Three cases of BSNS were retrieved, the histomorphology, immunophenotype and molecular genetics were analyzed with review of literature. Results: There were 2 male and 1 female patient aged 45, 29 and 40 years, respectively.Computed tomography and magnetic resonance imaging examinations showed a large polypoid mass occupying the sinonasal cavity in all 3 patients...
December 8, 2017: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
https://www.readbyqxmd.com/read/29221447/disruption-of-postnatal-folliculogenesis-and-development-of-ovarian-tumor-in-a-mouse-model-with-aberrant-transforming-growth-factor-beta-signaling
#8
Yang Gao, Xin Fang, David F Vincent, David W Threadgill, Laurent Bartholin, Qinglei Li
BACKGROUND: Transforming growth factor beta (TGFB) superfamily signaling is implicated in the development of sex cord-stromal tumors, a category of poorly defined gonadal tumors. The aim of this study was to determine potential effects of dysregulated TGFB signaling in the ovary using Cre recombinase driven by growth differentiation factor 9 (Gdf9) promoter known to be expressed in oocytes. METHODS: A mouse model containing constitutively active TGFBR1 (TGFBR1CA) using Gdf9-iCre (termed TGFBR1-CAG9Cre) was generated...
December 8, 2017: Reproductive Biology and Endocrinology: RB&E
https://www.readbyqxmd.com/read/29221208/higher-expression-of-foxos-correlates-to-better-prognosis-of-bladder-cancer
#9
Ying Zhang, Linpei Jia, Ying Zhang, Wei Ji, Hai Li
Background: We aimed to explore the expression of forkhead box class O (FOXO) and relations between expressions of FOXOs and clinicopathological characteristics and prognosis of bladder cancer. Methods: We enrolled a cohort of 276 patients with bladder cancer in our study. Expressions of FOXOs in bladder cancer tissue and adjacent tissue were measured by quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC). Correlations between expression of FOXOs and clinicopathological characteristics and prognosis were analyzed...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29217762/sirt6-is-a-target-of-regulation-by-ube3a-that-contributes-to-liver-tumorigenesis-in-an-anxa2-dependent-manner
#10
Saishruti Kohli, Abhishek Bhardwaj, Richa Kumari, Sanjeev Das
UBE3A is an E3 ubiquitin ligase well known for its role in the proteasomal degradation of p53 in human papillomavirus (HPV)-associated cancers. Here we report that UBE3A ubiquitylates and triggers degradation of the tumor suppressive sirtuin SIRT6 in hepatocellular carcinoma. UBE3A ubiquitylated the highly conserved Lys160 residue on SIRT6. FOXO1-mediated transcriptional repression of UBE3A was sufficient to stabilize SIRT6 and epigenetically repress ANXA2, a key mediator of UBE3A oncogenic function. Thus, UBE3A-mediated SIRT6 degradation promoted the proliferative capacity, migration potential and invasiveness of cells...
December 7, 2017: Cancer Research
https://www.readbyqxmd.com/read/29214757/clinical-and-cytogenetic-profiles-of-rhabdomyosarcoma-with-bone-marrow-involvement-in-korean-children-a-15-year-single-institution-experience
#11
Dong Hyun Lee, Chan Jeoung Park, Seongsoo Jang, Young Uk Cho, Jong Jin Seo, Ho Joon Im, Kyung Nam Koh, Kyung Ja Cho, Joon Seon Song, Eul Ju Seo
BACKGROUND: Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children. Alveolar RMS (ARMS) is characterized by FOXO1-related chromosomal translocations that result in a poorer clinical outcome compared with embryonal RMS (ERMS). Because the chromosomal features of RMS have not been comprehensively defined, we analyzed the clinical and laboratory data of childhood RMS patients and determined the clinical significance of chromosomal abnormalities in the bone marrow. METHODS: Fifty-one Korean patients with RMS <18 years of age treated between 2001 and 2015 were enrolled in this study...
March 2018: Annals of Laboratory Medicine
https://www.readbyqxmd.com/read/29213293/collagen-derived-dipeptide-prolyl-hydroxyproline-promotes-osteogenic-differentiation-through-foxg1
#12
Yoshifumi Kimira, Haruka Odaira, Kaho Nomura, Yuri Taniuchi, Naoki Inoue, Sachie Nakatani, Jun Shimizu, Masahiro Wada, Hiroshi Mano
Prolyl-hydroxyproline (Pro-Hyp) is one of the major constituents of collagen-derived dipeptides. We previously reported that Pro-Hyp promotes the differentiation of osteoblasts by increasing Runx2, osterix and Col1α1 mRNA expression levels. Here, to elucidate the mechanism of Pro-Hyp promotion of osteoblast differentiation, we focus on the involvement of Foxo1 in osteoblast differentiation via Runx2 regulation and the role of Foxg1 in Foxo1 regulation. The addition of Pro-Hyp had no effect on MC3T3-E1 cell proliferation in Foxo1- or Foxg1-knockdown cells...
2017: Cellular & Molecular Biology Letters
https://www.readbyqxmd.com/read/29212954/inhibition-of-akt-signaling-uncouples-t-cell-differentiation-from-expansion-for-receptor-engineered-adoptive-immunotherapy
#13
Christopher A Klebanoff, Joseph G Crompton, Anthony J Leonardi, Tori N Yamamoto, Smita S Chandran, Robert L Eil, Madhusudhanan Sukumar, Suman K Vodnala, Jinhui Hu, Yun Ji, David Clever, Mary A Black, Devikala Gurusamy, Michael J Kruhlak, Ping Jin, David F Stroncek, Luca Gattinoni, Steven A Feldman, Nicholas P Restifo
Adoptive immunotherapies using T cells genetically redirected with a chimeric antigen receptor (CAR) or T cell receptor (TCR) are entering mainstream clinical practice. Despite encouraging results, some patients do not respond to current therapies. In part, this phenomenon has been associated with infusion of reduced numbers of early memory T cells. Herein, we report that AKT signaling inhibition is compatible with CAR and TCR retroviral transduction of human T cells while promoting a CD62L-expressing central memory phenotype...
December 7, 2017: JCI Insight
https://www.readbyqxmd.com/read/29207597/inhibition-of-miro1-disturbs-mitophagy-and-pancreatic-%C3%AE-cell-function-interfering-insulin-release-via-irs-akt-foxo1-in-diabetes
#14
Lingling Chen, Chunyan Liu, Jianfeng Gao, Zhiwen Xie, Lawrence W C Chan, Damien J Keating, Yibin Yang, Jiazhong Sun, Fuling Zhou, Yongchang Wei, Xiuli Men, Sijun Yang
Mitochondrial function is essential to meet metabolic demand of pancreatic beta cells respond to high nutrient stress. Mitophagy is an essential component to normal pancreatic β-cell function and has been associated with β-cell failure in Type 2 diabetes (T2D). Our previous studies have indicated that mitochondrial Rho (Miro) GTPase-mediated mitochondrial dysfunction under high nutrient stress leads to NOD-like receptor 3 (NLRP3)-dependent proinflammatory responses and subsequent insulin resistance. However, the in vivo mechanism by which Miro1 underlies mitophagy has not been identified...
October 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/29207098/foxo1-is-crucial-in-glioblastoma-cell-tumorigenesis-and-regulates-the-expression-of-sirt1-to-suppress-senescence-in-the-brain
#15
Han Yan, Anhua Wu
In the present study, the role of Forkhead Box O1 (FOXO1) in glioblastoma (GBM) cell tumorigenesis was examined and the underlying mechanisms were investigated. Reverse transcription‑quantitative polymerase chain reaction and western blot analyses were used to analyze the expression of FOXO1 in GBM cell lines (LN18 and T98G) and tissues. Compared with the control groups, FOXO1 was significantly downregulated in the GBM tissues and GBM cell lines (P<0.05). The effects of the expression of FOXO1 on GBM cell proliferation and cell cycle were examined using flow cytometry...
November 23, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29203573/mechanisms-of-%C3%AE-cell-dedifferentiation-in-diabetes-recent-findings-and-future-research-directions
#16
Mohammed Bensellam, Jean-Christophe Jonas, D Ross Laybutt
Like all the cells of an organism, pancreatic β-cells originate from embryonic stem cells through a complex cellular process termed differentiation. Differentiation involves the coordinated and tightly controlled activation/repression of specific effectors and gene clusters in a time-dependent fashion thereby giving rise to particular morphological and functional cellular features. Interestingly, cellular differentiation is not a unidirectional process. Indeed, growing evidence suggests that under certain conditions, mature β-cells can lose, to various degrees, their differentiated phenotype and cellular identity and regress to a less differentiated or a precursor-like state...
December 4, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/29202868/sp-a2-contributes-to-mirna-mediated-sex-differences-in-response-to-oxidative-stress-pro-inflammatory-anti-apoptotic-and-anti-oxidant-pathways-are-involved
#17
George T Noutsios, Nithyananda Thorenoor, Xuesheng Zhang, David S Phelps, Todd M Umstead, Faryal Durrani, Joanna Floros
BACKGROUND: Human innate host defense molecules, surfactant protein A1 (SP-A1), and SP-A2 differentially affect the function and proteome of the alveolar macrophage (AM). We hypothesized that SP-A genes differentially regulate the AM miRNome. METHODS: Humanized transgenic mice expressing SP-A1 and SP-A2 were subjected to O3-induced oxidative stress (OxS) or filtered air (FA), AMs were isolated, and miRNA levels were measured. RESULTS: In SP-A2 males, we found significant changes in miRNome in terms of sex and sex-OxS effects, with 11 miRNAs differentially expressed under OxS...
December 4, 2017: Biology of Sex Differences
https://www.readbyqxmd.com/read/29202451/akt3-inhibits-adipogenesis-and-protects-from-diet-induced-obesity-via-signaling-pathway
#18
Liang Ding, Lifang Zhang, Sudipta Biswas, Rebecca C Schugar, J Mark Brown, Tatiana Byzova, Eugene Podrez
Three Akt isoforms, encoded by 3 separate genes, are expressed in mammals. While the roles of Akt1 and Akt2 in metabolism are well established, it is not yet known whether Akt3 plays a role in metabolic diseases. We now report that Akt3 protects mice from high-fat diet-induced obesity by suppressing an alternative pathway of adipogenesis via with no lysine protein kinase-1 (WNK1) and serum/glucocorticoid-inducible kinase 1 (SGK1). We demonstrate that Akt3 specifically phosphorylates WNK1 at T58 and promotes its degradation via the ubiquitin-proteasome pathway...
November 16, 2017: JCI Insight
https://www.readbyqxmd.com/read/29201212/anti-aging-effect-of-fullerenol-on-skin-aging-through-derived-stem-cells-in-a-mouse-model
#19
Wei Li, Ning Li, Bing Sui, Daping Yang
Fullerenol is similar to graphite in terms of structure. In the present study, the anti-aging effect of fullerenol on skin through derived stem cells in a mouse model was assessed and the potential mechanism of fullerenol was investigated. The anti-aging effect of fullerenol effectively inhibited the retention rate of transplanted adipose-derived stem cells and increased the thickness of the dermal portion of skin and collagen ratio in mice. The effect of fullerenol on the proliferation of stem cells was observed...
November 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29191913/metabolic-reprogramming-of-human-cd8-memory-t-cells-through-loss-of-sirt1
#20
Mark Y Jeng, Philip A Hull, Mingjian Fei, Hye-Sook Kwon, Chia-Lin Tsou, Herb Kasler, Che-Ping Ng, David E Gordon, Jeffrey Johnson, Nevan Krogan, Eric Verdin, Melanie Ott
The expansion of CD8+CD28- T cells, a population of terminally differentiated memory T cells, is one of the most consistent immunological changes in humans during aging. CD8+CD28- T cells are highly cytotoxic, and their frequency is linked to many age-related diseases. As they do not accumulate in mice, many of the molecular mechanisms regulating their fate and function remain unclear. In this paper, we find that human CD8+CD28- T cells, under resting conditions, have an enhanced capacity to use glycolysis, a function linked to decreased expression of the NAD+-dependent protein deacetylase SIRT1...
November 30, 2017: Journal of Experimental Medicine
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