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https://www.readbyqxmd.com/read/29149835/forkhead-transcription-factors-formulating-a-foxo-target-for-cognitive-loss
#1
Kenneth Maiese
BACKGROUND: With almost 47 million individuals worldwide suffering from some aspect of dementia, it is clear that cognitive loss impacts a significant proportion of the global population. Unfortunately, definitive treatments to resolve or prevent the onset of cognitive loss are limited. In most cases such care is currently non-existent prompting the need for novel treatment strategies. METHODS: Mammalian forkhead transcription factors of the O class (FoxO) are one such avenue of investigation that offer an exciting potential to bring new treatments forward for disorders that involve cognitive loss...
November 15, 2017: Current Neurovascular Research
https://www.readbyqxmd.com/read/29147649/knockdown-of-sirt1-suppresses-bladder-cancer-cell-proliferation-and-migration-and-induces-cell-cycle-arrest-and-antioxidant-response-through-foxo3a-mediated-pathways
#2
Qingxuan Hu, Gang Wang, Jianping Peng, Guofeng Qian, Wei Jiang, Conghua Xie, Yu Xiao, Xinghuan Wang
Bladder cancer (BCa) is one of the most common tumors, but its underlying mechanism has not been fully clarified. Our transcriptome analysis suggested a close link of Sirtuins, Peroxisome Proliferator-Activated Receptor (PPAR), cell cycle regulation, reactive oxygen species (ROS) metabolism, and Forkhead Box Class O (FOXO) signaling pathway in BCa. SIRT1 is a key member of Sirtuins, playing important roles in aging and energy metabolism, which has been reported to be involved in various metabolic diseases and tumors...
2017: BioMed Research International
https://www.readbyqxmd.com/read/29143154/deciphering-the-molecular-events-during-arsenic-induced-transcription-signal-cascade-activation-in-cellular-milieu
#3
REVIEW
Harishkumar Madhyastha, Radha Madhyastha, Yuichi Nakajima, Masugi Maruyama
Anthropogenic sources of arsenic poses and creates unintentional toxico-pathological concerns to humans in many parts of the world. The understanding of toxicity of this metalloid, which shares properties of both metal and non-metal is principally structured on speciation types and holy grail of toxicity prevention. Visible symptoms of arsenic toxicity include nausea, vomiting, diarrhea and abdominal pain. In this review, we focused on the dermal cell stress caused by trivalent arsenic trioxide and pentavalent arsanilic acid...
November 15, 2017: Biometals: An International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine
https://www.readbyqxmd.com/read/29138552/sirt1-and-foxo1-mrna-expression-in-pbmc-correlates-to-physical-activity-in-copd-patients
#4
Chihiro Taka, Ryuji Hayashi, Kazuki Shimokawa, Kotaro Tokui, Seisuke Okazawa, Kenta Kambara, Minehiko Inomata, Toru Yamada, Shoko Matsui, Kazuyuki Tobe
Background: Physical activity (PA) is considered as one of the most important prognostic predictors in chronic obstructive pulmonary disease (COPD) patients. Longevity gene, SIRT1, is reported to be involved in the pathogenesis of COPD by regulating the signaling pathways of oxidative stress, inflammation, and aging. We hypothesize that SIRT1 and related genes are also associated with the benefits of PA in COPD patients. Methods: Eighteen COPD outpatients were enrolled in this study, and their PA level was assessed with an accelerometer...
2017: International Journal of Chronic Obstructive Pulmonary Disease
https://www.readbyqxmd.com/read/29131127/pleiotropic-effects-of-white-willow-bark-and-1-2-decanediol-on-human-adult-keratinocytes
#5
Eleonora Bassino, Franco Gasparri, Luca Munaron
BACKGROUND: Acne vulgaris is a common skin defect, usually occurring during adolescence, but often it can persist in adults leaving permanent face scarring. Acne is usually treated with topical drugs, oral antibiotics, retinoids, and hormonal therapies, but medicinal plants are increasingly employed. OBJECTIVE: To investigate the protective role of white willow bark (WWB) and 1,2-decanediol (DD) on the damage caused by lipopolysaccharides (LPS) on human adult keratinocytes (HaCaT)...
November 8, 2017: Skin Pharmacology and Physiology
https://www.readbyqxmd.com/read/29128891/prmt1-promotes-hyperglycemia-in-a-foxo1-dependent-manner-affecting-glucose-metabolism-during-hypobaric-hypoxia-exposure-in-rat-model
#6
Susovon Bayen, Supriya Saini, Priya Gaur, Arul Joseph Duraisamy, Alpesh Kumar Sharma, Karan Pal, Praveen Vats, Shashi Bala Singh
PURPOSE: High-altitude (HA) environment causes changes in cellular metabolism among unacclimatized humans. Previous studies have revealed that insulin-dependent activation of protein kinase B (Akt) regulates metabolic processes via discrete transcriptional effectors. Moreover, protein arginine methyltransferase (PRMT)1-dependent arginine modification of forkhead box other (FoxO)1 protein interferes with Akt-dependent phosphorylation. The present study was undertaken to test the involvement of PRMT1 on FoxO1 activation during hypobaric hypoxia (HH) exposure in rat model...
November 11, 2017: Endocrine
https://www.readbyqxmd.com/read/29119376/regulatory-effects-of-antitumor-agent-matrine-on-foxo-and-pi3k-akt-pathway-in-castration-resistant-prostate-cancer-cells
#7
Qi Li, Hai Huang, Zheng He, Yi Sun, Yufeng Tang, Xiaohong Shang, Chengbin Wang
We previously demonstrated that matrine could inhibit the proliferating, migrating, as well as invading processes of both PC-3 and DU145 cells. However, the underlying molecular mechanisms have not yet been clearly defined. In this study, using various techniques such as high throughput sequencing technology, bioinformatics, quantitative real-time PCR, and immunoblot analysis, we aimed to understand whether matrine serves as a novel regulator of FOXO and PI3K-AKT signaling pathway. DU145 and PC-3 cell lines were cultured for 24 h in vitro...
November 7, 2017: Science China. Life Sciences
https://www.readbyqxmd.com/read/29103953/wnt-mediated-regulation-of-foxo1-constitutes-a-critical-axis-maintaining-pubertal-mammary-stem-cell-homeostasis
#8
Amulya Sreekumar, Michael J Toneff, Eajer Toh, Kevin Roarty, Chad J Creighton, George K Belka, Dong-Kee Lee, Jianming Xu, Lewis A Chodosh, JoAnne S Richards, Jeffrey M Rosen
Puberty is characterized by dynamic tissue remodeling in the mammary gland involving ductal elongation, resolution into the mature epithelial bilayer, and lumen formation. To decipher the cellular mechanisms underlying these processes, we studied the fate of putative stem cells, termed cap cells, present in terminal end buds of pubertal mice. Employing a p63(CreERT2)-based lineage-tracing strategy, we identified a unipotent fate for proliferative cap cells that only generated cells with basal features. Furthermore, we observed that dislocated "cap-in-body" cells underwent apoptosis, which aided lumen formation during ductal development...
October 31, 2017: Developmental Cell
https://www.readbyqxmd.com/read/29102406/keeping-neurons-young-and-foxy-foxos-promote-neuronal-plasticity
#9
REVIEW
Colleen N McLaughlin, Heather T Broihier
Any adult who has tried to take up the piano or learn a new language is faced with the sobering realization that acquiring such skills is more challenging as an adult than as a child. Neuronal plasticity, or the malleability of brain circuits, declines with age. Young neurons tend to be more adaptable and can alter the size and strength of their connections more readily than can old neurons. Myriad circuit- and synapse-level mechanisms that shape plasticity have been identified. Yet, molecular mechanisms setting the overall competence of young neurons for distinct forms of plasticity remain largely obscure...
November 1, 2017: Trends in Genetics: TIG
https://www.readbyqxmd.com/read/29079711/histone-deacetylase-inhibition-enhances-the-antitumor-activity-of-a-mek-inhibitor-in-lung-cancer-cells-harboring-ras-mutations
#10
Tadaaki Yamada, Joseph M Amann, Azusa Tanimoto, Hirokazu Taniguchi, Takehito Shukuya, Cynthia Timmers, Seiji Yano, Konstantin Shilo, David P Carbone
Non-small-cell lung cancer (NSCLC) can be identified by precise molecular subsets based on genomic alterations that drive tumorigenesis and include mutations in EGFR, KRAS, and various ALK fusions. However, despite effective treatments for EGFR and ALK, promising therapeutics have not been developed for patients with KRAS mutations. It has been reported that one way the RAS-ERK pathway contributes to tumorigenesis is by affecting stability and localization of FOXO3a protein, an important regulator of cell death and the cell cycle...
October 27, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29075860/dna-mismatch-repair-deficiency-promotes-genomic-instability-in-a-subset-of-papillary-thyroid-cancers
#11
Mahsa Javid, Thanyawat Sasanakietkul, Norman G Nicolson, Courtney E Gibson, Glenda G Callender, Reju Korah, Tobias Carling
BACKGROUND: Efficient DNA damage repair by MutL-homolog DNA mismatch repair (MMR) enzymes, MLH1, MLH3, PMS1 and PMS2, are required to maintain thyrocyte genomic integrity. We hypothesized that persistent oxidative stress and consequent transcriptional dysregulation observed in thyroid follicles will lead to MMR deficiency and potentiate papillary thyroid tumorigenesis. METHODS: MMR gene expression was analyzed by targeted microarray in 18 papillary thyroid cancer (PTC), 9 paracarcinoma normal thyroid (PCNT) and 10 normal thyroid (NT) samples...
October 11, 2017: World Journal of Surgery
https://www.readbyqxmd.com/read/29072689/mir-629-promotes-human-pancreatic-cancer-progression-by-targeting-foxo3
#12
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/29069829/the-mir-486-5p-plays-a-causative-role-in-prostate-cancer-through-negative-regulation-of-multiple-tumor-suppressor-pathways
#13
Yang Yang, Changwei Ji, Suhan Guo, Xin Su, Xiaozhi Zhao, Shiwei Zhang, Guangxiang Liu, Xuefeng Qiu, Qing Zhang, Hongqian Guo, Huimei Chen
MicroRNAs have been broadly implicated in cancer, but their exact function and mechanism in carcinogenesis remain poorly understood. Aberrant miR-486-5p expression is frequently found in human cancers. Here we showed a significant overexpression of miR-486-5p in prostate cancer compared with that in normal tissue and cells, and we proposed that altered expression of miR-486-5p in the prostate contributed to prostate cancer. Firstly, miR-486-5p inhibition expression reduced prostate cancercell proliferation, migration, and colonization in vitro and prostate tumor development in vivo...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29065837/usp7-target-validation-and-drug-discovery-for-cancer-therapy
#14
Jin Zhou, Jinzheng Wang, Chao Chen, Haoliang Yuan, Xiaoan Wen, Hongbin Sun
BACKGROUND: USP7 (ubiquitin specific protease 7, also known as HAUSP) is one of the deubiquitinating enzymes (DUB) that reverse ubiquitination and spare substrate proteins from degradation. METHODS: After a brief introduction of ubiquitin-proteasome system (UPS) and human DUB, this review focuses on the structural and functional complexity of USP7 in tumor development and progression. Afterwards, USP7's physiological regulatory mechanisms and manipulation strategies are elaborated...
October 20, 2017: Medicinal Chemistry
https://www.readbyqxmd.com/read/29064820/identification-of-polymorphisms-in-cancer-patients-that-differentially-affect-survival-with-age
#15
Aoife Doherty, Yelena Kernogitski, Alexander M Kulminski, João Pedro de Magalhães
The World Health Organization predicts that the proportion of the world's population over 60 will almost double from 12% to 22% between 2015 and 2050. Ageing is the biggest risk factor for cancer, which is a leading cause of deaths worldwide. Unfortunately, research describing how genetic variants affect cancer progression commonly neglects to account for the ageing process. Herein is the first systematic analysis that combines a large longitudinal data set with a targeted candidate gene approach to examine the effect of genetic variation on survival as a function of age in cancer patients...
October 20, 2017: Aging
https://www.readbyqxmd.com/read/29063832/daf-16-foxo-promotes-gluconeogenesis-and-trehalose-synthesis-during-starvation-to-support-survival
#16
Jonathan D Hibshman, Alexander E Doan, Brad T Moore, Rebecca Ew Kaplan, Anthony Hung, Amy K Webster, Dhaval P Bhatt, Rojin Chitrakar, Matthew D Hirschey, L Ryan Baugh
daf-16/FoxO is required to survive starvation in Caenorhabditis elegans, but how daf-16IFoxO promotes starvation resistance is unclear. We show that daf-16/FoxO restructures carbohydrate metabolism by driving carbon flux through the glyoxylate shunt and gluconeogenesis and into synthesis of trehalose, a disaccharide of glucose. Trehalose is a well-known stress protectant, capable of preserving membrane organization and protein structure during abiotic stress. Metabolomic, genetic, and pharmacological analyses confirm increased trehalose synthesis and further show that trehalose not only supports survival as a stress protectant but also serves as a glycolytic input...
October 24, 2017: ELife
https://www.readbyqxmd.com/read/29056338/selective-inhibition-of-foxo1-activator-repressor-balance-modulates-hepatic-glucose-handling
#17
Fanny Langlet, Rebecca A Haeusler, Daniel Lindén, Elke Ericson, Tyrrell Norris, Anders Johansson, Joshua R Cook, Kumiko Aizawa, Ling Wang, Christoph Buettner, Domenico Accili
Insulin resistance is a hallmark of diabetes and an unmet clinical need. Insulin inhibits hepatic glucose production and promotes lipogenesis by suppressing FOXO1-dependent activation of G6pase and inhibition of glucokinase, respectively. The tight coupling of these events poses a dual conundrum: mechanistically, as the FOXO1 corepressor of glucokinase is unknown, and clinically, as inhibition of glucose production is predicted to increase lipogenesis. Here, we report that SIN3A is the insulin-sensitive FOXO1 corepressor of glucokinase...
November 2, 2017: Cell
https://www.readbyqxmd.com/read/29052315/identification-and-evolution-of-latrophilin-receptor-gene-involved-in-tribolium-castaneum-devolopment-and-female-fecundity
#18
Shanshan Gao, Xing Liu, Juanjuan Liu, Wenfeng Xiong, Xiaowen Song, Wei Wu, Luting Wei, Bin Li
Latrophilins (LPHs) are adhesion G-protein-coupled receptors comprising three paralogous forms (LPH-1, LPH-2, and LPH-3) and known receptors for α-latrotoxin, which are involved in growth, development, adaptability, and schizophrenia and other diseases in vertebrates. However, the functions of LPH are poorly understood in most insects. Here, phylogenetic and synteny analysis indicated that LPH-1 and LPH-3 evolved separately from a common ancestor LPH-2. Then, latrophilin (Tclph) was cloned in Tribolium castaneum, and three alternatively spliced transcripts (Tclpha, Tclphb and Tclphc) were identified...
October 20, 2017: Genesis: the Journal of Genetics and Development
https://www.readbyqxmd.com/read/29045932/modulation-of-sestrin-confers-protection-to-cr-vi-induced-neuronal-cell-death-in-drosophila-melanogaster
#19
Pallavi Singh, D Kar Chowdhuri
Increased oxidative stress is one of the major causes of hexavalent chromium [Cr(VI)], a heavy metal with diverse applications and environmental presence, induced neuronal adversities in exposed organism including Drosophila. Sestrin (sesn), an oxidative stress responsive gene, emerges as a novel player in the management of oxidative stress response. It is reported to be regulated by Target of rapamycin (TOR) and the former regulates autophagy and plays an important role in the prevention of neurodegeneration...
October 7, 2017: Chemosphere
https://www.readbyqxmd.com/read/29034337/new-biomarkers-of-post-settlement-growth-in-the-sea-urchin-strongylocentrotus-purpuratus
#20
Alyaa Elsaid Abdelaziz Fadl, Magdy Elsayed Mahfouz, Mona Mabrouk Taha El-Gamal, Andreas Heyland
Some sea urchins, including the purple sea urchin Strongylocentrotus purpuratus, have been successfully used in aquaculture, but their slow growth and late reproduction are challenging to overcome when developing efficient aquaculture production techniques. S. purpuratus develops via an indirect life history that is characterized by a drastic settlement process at the end of a larval period that lasts for several weeks. During this transition, the bilateral larva is transformed into a pentaradial juvenile, which will start feeding and growing in the benthic habitat...
October 2017: Heliyon
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