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target of rapamycin

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https://www.readbyqxmd.com/read/28643873/increased-expression-of-immuno-proteasome-subunits-during-epileptogenesis-is-attenuated-by-inhibition-of-the-mammalian-target-of-rapamycin-pathway
#1
Diede W M Broekaart, Jackelien van Scheppingen, Karlijne W Geijtenbeek, Mark R J Zuidberg, Jasper J Anink, Johannes C Baayen, Angelika Mühlebner, Eleonora Aronica, Jan A Gorter, Erwin A van Vliet
OBJECTIVE: Inhibition of the mammalian target of rapamycin (mTOR) pathway reduces epileptogenesis in various epilepsy models, possibly by inhibition of inflammatory processes, which may include the proteasome system. To study the role of mTOR inhibition in the regulation of the proteasome system, we investigated (immuno)proteasome expression during epileptogenesis, as well as the effects of the mTOR inhibitor rapamycin. METHODS: The expression of constitutive (β1, β5) and immunoproteasome (β1i, β5i) subunits was investigated during epileptogenesis using immunohistochemistry in the electrical post-status epilepticus (SE) rat model for temporal lobe epilepsy (TLE)...
June 23, 2017: Epilepsia
https://www.readbyqxmd.com/read/28641881/peripheral-blood-regulatory-t-cell-counts-as-a-predictive-biomarker-for-the-outcome-of-kidney-transplant-a-systematic-review
#2
Francisco Herrera-Gómez, Mónica Vásquez-Seoane, Waldo Del Aguila, Débora Martín-García, Álvaro Maurtua-Briseño Meiggs, Anunciación González-López, Beatriz Andrés-Martín, Álvaro Nava-Rebollo, Fernando Casquero-Fernández, Pilar Pascual-Núñez, Jesús Grande-Villoria, Jesús Bustamante-Bustamante, Carlos Ochoa-Sangrador, Claude Lambert, Alicia Mendiluce-Herrero
BACKGROUND AND OBJECTIVE: Circulating regulatory T cells could become a suitable biomarker for kidney recipients. The objective of this study was to evaluate the effect of mammalian target of rapamycin (mTOR) inhibitors on regulatory T cell numbers, and the clinical interest of this effect. MATERIAL AND METHODS: Systematic review of published and unpublished studies. Worldwide databases or repositories. Randomised controlled trials and cohort studies comparing regulatory T cell counts and rejection episodes between patients with and without mTOR inhibitors were searched...
June 19, 2017: Medicina Clínica
https://www.readbyqxmd.com/read/28641488/uca1-involved-in-the-metformin-regulated-bladder-cancer-cell-proliferation-and-glycolysis
#3
Tian Li, Xiangzhou Sun, Xianhan Jiang
Despite great scientific advances have been achieved in cancer treatment in recent years, the death rate of bladder cancer has been staying at a high level. Metformin, a widely-used and low-cost diabetes medicine, might have the potential of anticancer. The aim of this study was to evaluate the effects of metformin on bladder cancer cells and to identify potential molecular targets and signaling pathways. Bladder cancer 5637 cells transfected with either pcDNA/UCA1 vector or pcDNA3.1 empty vector were treated with various doses of metformin for different periods of time, and then cell proliferation and glycolysis were assessed...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28641136/age-exacerbates-abnormal-protein-expression-in-a-mouse-model-of-down-syndrome
#4
Md Mahiuddin Ahmed, Aaron Block, Suhong Tong, Muriel T Davisson, Katheleen J Gardiner
The Ts65Dn is a popular mouse model of Down syndrome (DS). It displays DS-relevant features of learning/memory deficits and age-related loss of functional markers in basal forebrain cholinergic neurons. Here we describe protein expression abnormalities in brain regions of 12-month-old male Ts65Dn mice. We show that the magnitudes of abnormalities of human chromosome 21 and non-human chromosome 21 orthologous proteins are greater at 12 months than at ∼6 months. Age-related exacerbations involve the number of components affected in the mechanistic target of rapamycin pathway, the levels of components of the mitogen-activated protein kinase pathway, and proteins associated with Alzheimer's disease...
May 10, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28639951/metabolic-abnormalities-and-oxidative-stress-in-lupus
#5
Yaima L Lightfoot, Luz P Blanco, Mariana J Kaplan
PURPOSE OF REVIEW: Upon antigen exposure, immune cells rely on cell-specific metabolic pathways to mount an efficient immune response. In autoimmunity, failure in critical metabolic checkpoints may lead to immune cell hyperactivation and tissue damage. Oxidative stress in autoimmune patients can also contribute to immune dysregulation and injury to the host. Recent insights into the immune cell metabolism signatures, specifically associated with systemic lupus erythematosus (SLE) and the consequences of heightened oxidative stress in patients, are discussed herein...
July 20, 2017: Current Opinion in Rheumatology
https://www.readbyqxmd.com/read/28639903/targeting-the-mtor-pathway-in-breast-cancer
#6
Jia Liu, Hui-Qing Li, Fu-Xia Zhou, Jie-Wen Yu, Ling Sun, Zhong-Hou Han
Mechanistic target of rapamycin controls cell growth, metabolism, and aging in response to nutrients, cellular energy stage, and growth factors. In cancers including breast cancer, mechanistic target of rapamycin is frequently upregulated. Blocking mechanistic target of rapamycin with rapamycin, first-generation and second-generation mechanistic target of rapamycin inhibitors, called rapalogs, have shown potent reduction of breast cancer tumor growth in preclinical models and clinical trials. In this review, we summarize the fundamental role of the mechanistic target of rapamycin pathway in driving breast tumors...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28639902/mild-hyperthermia-enhances-sensitivity-of-gastric-cancer-cells-to-chemotherapy-through-reactive-oxygen-species-induced-autophagic-death
#7
Ming-Chen Ba, Hui Long, Shu-Zhong Cui, Yuan-Feng Gong, Zhao-Fei Yan, Shuai Wang, Yin-Bing Wu
Mild hyperthermia enhances anti-cancer effects of chemotherapy, but the precise biochemical mechanisms involved are not clear. This study was carried out to investigate whether mild hyperthermia sensitizes gastric cancer cells to chemotherapy through reactive oxygen species-induced autophagic death. In total, 20 BABL/c mice of MKN-45 human gastric cancer tumor model were divided into hyperthermia + chemotherapy group, hyperthermia group, chemotherapy group, N-acetyl-L-cysteine group, and mock group. Reactive oxygen species production and expression of autophagy-related genes Beclin1, LC3B, and mammalian target of rapamycin were determined...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28638821/the-tor-signaling-pathway-in-spatial-and-temporal-control-of-cell-size-and-growth
#8
REVIEW
Suam Gonzalez, Charalampos Rallis
Cell size is amenable by genetic and environmental factors. The highly conserved nutrient-responsive Target of Rapamycin (TOR) signaling pathway regulates cellular metabolic status and growth in response to numerous inputs. Timing and duration of TOR pathway activity is pivotal for both cell mass built up as well as cell cycle progression and is controlled and fine-tuned by the abundance and quality of nutrients, hormonal signals, growth factors, stress, and oxygen. TOR kinases function within two functionally and structurally discrete multiprotein complexes, TORC1 and TORC2, that are implicated in temporal and spatial control of cell size and growth respectively; however, recent data indicate that such functional distinctions are much more complex...
2017: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/28638450/osteopontin-is-critical-for-hyperactive-mtor-induced-tumorigenesis-in-oral-squamous-cell-carcinoma
#9
Ning Gan, Sihai Zou, Wenming Hang, Deqin Yang, Xuemei Zhang, Yibing Yin
Mechanistic target of rapamycin (mTOR) plays a critical role in the development of oral squamous cell carcinoma (OSCC), but the underlying mechanisms remain poorly understood. Here we have demonstrated that the expression of osteopontin (OPN) was dramatically up-regulated in OSCC tissues and cell lines. Moreover, reduction of OPN suppressed cell proliferation, colony formation, and in vivo tumorigenic ability of OSCC cell lines Tca8113. In addition, there was a strong positive correlation between mTORC1 activity and OPN expression in OSCC tissues and cell lines...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28638431/erzhi-pill%C3%A2-repairs-experimental-liver-injury-via-tsc-mtor-signaling-pathway-inhibiting-excessive-apoptosis
#10
Bu-Gao Zhou, Hai-Mei Zhao, Xiu-Yun Lu, Xin Wang, Yong Zou, Rong Xu, Hai-Yang Yue, Yi Liu, Zheng-Yun Zuo, Duan-Yong Liu
The present study aimed to investigate the mechanism of hepatoprotective effect of Erzhi Pill (EZP) on the liver injury via observing TSC/mTOR signaling pathway activation. The experimental liver injury was induced by 2-acetylaminofluorene (2-AAF) treatment combined with partial hepatectomy (PH). EZP treated 2-AAF/PH-induced liver injury by the therapeutic and prophylactic administration. After the administration of EZP, the activities of aspartic transaminase (AST), alanine aminotransferase (ALT), alkaline phosphatase (AKP), and gamma-glutamyl transpeptidase (γ-GT) were decreased, followed by the decreased levels of hepatocyte apoptosis and caspase-3 expression...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28638350/branched-chain-amino-acid-ingestion-stimulates-muscle-myofibrillar-protein-synthesis-following-resistance-exercise-in-humans
#11
Sarah R Jackman, Oliver C Witard, Andrew Philp, Gareth A Wallis, Keith Baar, Kevin D Tipton
The ingestion of intact protein or essential amino acids (EAA) stimulates mechanistic target of rapamycin complex-1 (mTORC1) signaling and muscle protein synthesis (MPS) following resistance exercise. The purpose of this study was to investigate the response of myofibrillar-MPS to ingestion of branched-chain amino acids (BCAAs) only (i.e., without concurrent ingestion of other EAA, intact protein, or other macronutrients) following resistance exercise in humans. Ten young (20.1 ± 1.3 years), resistance-trained men completed two trials, ingesting either 5...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28637240/tfeb-activation-restores-migration-ability-to-tsc1-deficient-adult-neural-stem-progenitor-cells
#12
Alessandro Magini, Alice Polchi, Danila Di Meo, Giuseppina Mariucci, Krizia Sagini, Federico De Marco, Tommaso Cassano, Stefano Giovagnoli, Diego Dolcetta, Carla Emiliani
Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder caused by mutations in either of two genes, TSC1 or TSC2, resulting in the constitutive activation of the mammalian target of rapamycin complex 1 (mTORC1). mTOR inhibitors are now considered the treatment of choice for TSC disease. A major pathological feature of TSC is the development of subependymal giant cell astrocytomas (SEGAs) in the brain. Nowadays, it is thought that SEGAs could be a consequence of aberrant aggregation and migration of neural stem/progenitor cells (NSPCs)...
June 14, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28636966/the-torc-that-gets-the-gc-cycling
#13
Elissa K Deenick, Stuart G Tangye
The signaling pathways regulating positive selection in germinal centers (GCs) are incompletely understood. Ersching et al. (2017) identify a critical but temporal role for the action of the kinase mechanistic target of rapamycin complex (mTORC1), which promotes key changes in GC B cells and thereby facilitates affinity maturation.
June 20, 2017: Immunity
https://www.readbyqxmd.com/read/28636954/germinal-center-selection-and-affinity-maturation-require-dynamic-regulation-of-mtorc1-kinase
#14
Jonatan Ersching, Alejo Efeyan, Luka Mesin, Johanne T Jacobsen, Giulia Pasqual, Brian C Grabiner, David Dominguez-Sola, David M Sabatini, Gabriel D Victora
During antibody affinity maturation, germinal center (GC) B cells cycle between affinity-driven selection in the light zone (LZ) and proliferation and somatic hypermutation in the dark zone (DZ). Although selection of GC B cells is triggered by antigen-dependent signals delivered in the LZ, DZ proliferation occurs in the absence of such signals. We show that positive selection triggered by T cell help activates the mechanistic target of rapamycin complex 1 (mTORC1), which promotes the anabolic program that supports DZ proliferation...
June 20, 2017: Immunity
https://www.readbyqxmd.com/read/28635136/knockdown-of-tor-causing-ovarian-diapause-in-a-genetically-stable-brachypterous-strain-of-nilaparvata-lugens
#15
Fangzhou Liu, Kaiyin Li, Wanlun Cai, Jing Zhao, Yulan Zou, Hongxia Hua
Brown planthopper (BPH), Nilaparvata lugens (Stål) (Hemiptera: Delphacidae), is one of the most damaging pests of rice crops. BPH is a migratory insect with a delayed ovarian development in migrants classified as reproductive diapause. The molecular mechanism of reproductive diapause remains unclear, although we suspect it might be regulated by one or more nutrient signaling pathways. The target of rapamycin (TOR) pathway regulates cell growth in response to nutritional information, which raised a hypothesis that TOR mediates BPH reproductive diapause...
June 20, 2017: Archives of Insect Biochemistry and Physiology
https://www.readbyqxmd.com/read/28634872/predictive-markers-of-response-to-everolimus-and-sunitinib-in-neuroendocrine-tumors
#16
Diana Martins, Francesca Spada, Ioana Lambrescu, Manila Rubino, Chiara Cella, Bianca Gibelli, Chiara Grana, Dario Ribero, Emilio Bertani, Davide Ravizza, Guido Bonomo, Luigi Funicelli, Eleonora Pisa, Dario Zerini, Nicola Fazio
Neuroendocrine tumors (NETs) represent a large and heterogeneous group of malignancies with various biological and clinical characteristics, depending on the site of origin and the grade of tumor proliferation. In NETs, as in other cancer types, molecularly targeted therapies have radically changed the therapeutic landscape. Recently two targeted agents, the mammalian target of rapamycin inhibitor everolimus and the tyrosine kinase inhibitor sunitinib, have both demonstrated significantly prolonged progression free survival in patients with advanced pancreatic NETs...
June 21, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28634408/a-tightly-regulated-il-22-response-maintains-immune-functions-and-homeostasis-in-systemic-viral-infection
#17
Panpan Yi, Yuejin Liang, Denley Ming Kee Yuan, Zuliang Jie, Zakari Kwota, Yan Chen, Yingzi Cong, Xuegong Fan, Jiaren Sun
Interleukin-22 (IL-22) plays an important role in host immunity and tissue homeostasis in infectious and inflammatory diseases. However, the function and regulation of IL-22 in viral infection remain largely unknown. Here, we report that viral infection triggered early IL-22 production from the liver and lymphoid organs. γδ T cells are the main immune cells to produce IL-22 in the liver, a process mediated by the IL-23/phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin complex 1 (mTORC1) signaling pathway...
June 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28632947/pimozide-reduces-toxic-forms-of-tau-in-tauc3-mice-via-ampk-mediated-autophagy
#18
YoungDoo Kim, Eun Il Jeong, Jihoon Nah, Seung-Min Yoo, WonJae Lee, Youbin Kim, Seowon Moon, Se-Hoon Hong, Yong-Keun Jung
In neurodegenerative diseases like Alzheimer's disease (AD), tau is hyperphosphorylated and forms aggregates and neurofibrillary tangles in affected neurons. Autophagy is critical to clear the aggregates of disease-associated proteins and is often altered in patients and animal models of AD. Because mTOR (mechanistic target of rapamycin) negatively regulates autophagy and is hyperactive in the brains of patients with AD, mTOR is an attractive therapeutic target for AD. However, pharmacological strategies to increase autophagy by targeting mTOR inhibition cause various side effects...
June 20, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28629935/a-dicre-recombinase-based-system-for-inducible-expression-in-leishmania-major
#19
Renato E R S Santos, Gabriel L A Silva, Elaine V Santos, Samuel M Duncan, Jeremy C Mottram, Jeziel D Damasceno, Luiz R O Tosi
Here we present the establishment of an inducible system based on the dimerizable Cre recombinase (DiCre) for controlled gene expression in the protozoan parasite Leishmania. Rapamycin-induced DiCre activation promoted efficient flipping and expression of gene products in a time and dose-dependent manner. The DiCre flipping activity induced the expression of target genes from both integrated and episomal contexts broadening the applicability of the system. We validated the system by inducing the expression of both full length and truncated forms of the checkpoint protein Rad9, which revealed that the highly divergent C-terminal domain of Rad9 is necessary for proper subcellular localization...
June 16, 2017: Molecular and Biochemical Parasitology
https://www.readbyqxmd.com/read/28629357/xuefuzhuyu-decoction-protected-cardiomyocytes-against-hypoxia-reoxygenation-injury-by-inhibiting-autophagy
#20
Xiaowen Shi, Haiyan Zhu, Yuanyuan Zhang, Mingmei Zhou, Danli Tang, Huamin Zhang
BACKGROUND: XuefuZhuyu decoction (XFZY) is a well-known traditional Chinese herbal medicine for the treatment of various cardiovascular diseases, such as unstable angina pectoris and myocardial ischemia-reperfusion injury. However, the mechanism by which XFZY contributes to the amelioration of cardiac injury remains unclear. METHODS: H9C2 cells were cultured under the hypoxic condition for 10 h and reoxygenated for 2 h. In the presence of various concentrations of XFZY for 12 h, the cell viability was measured by MTT assay...
June 19, 2017: BMC Complementary and Alternative Medicine
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