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https://www.readbyqxmd.com/read/28230853/mesenchymal-stromal-cells-inhibit-cd25-expression-via-the-mtor-pathway-to-potentiate-t-cell-suppression
#1
Hyun Seung Yoo, Kyuheon Lee, Kwangmin Na, Yong Xu Zhang, Hyun-Ja Lim, TacGhee Yi, Sun U Song, Myung-Shin Jeon
Mesenchymal stromal cells (MSCs) are known to suppress T-cell activation and proliferation. Several studies have reported that MSCs suppress CD25 expression in T cells. However, the molecular mechanism underlying MSC-mediated suppression of CD25 expression has not been fully examined. Here, we investigated the mTOR pathway, which is involved in CD25 expression in T cells. We showed that MSCs inhibited CD25 expression, which was restored in the presence of an inducible nitric oxide synthase (iNOS) inhibitor...
February 23, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28230643/mtor-inhibition-clinical-transplantation-pancreas-islet
#2
Thierry Berney, Axel Andres, Christian Toso, Pietro Majno, Jean-Paul Squifflet
This brief overview discusses the beneficial and deleterious effects of mTOR inhibitors on beta-cells, and how sirolimus- and everolimus-based immunosuppression have impacted on practices and outcomes of pancreas and islet transplantation. Sirolimus was the cornerstone of immunosuppressive regimens in islet transplantation at the turn of the millenium, but utilization of mTOR inhibitors has progressively decreased from >80% to <50% of islet transplant recipients in more recent years. For whole pancreas transplantation, mTOR inhibitors were used in approximately 20% of patients in the early 2000s, but this dropped over the years to <10% currently...
February 23, 2017: Transplantation
https://www.readbyqxmd.com/read/28230639/mammalian-target-of-rapamycin-inhibition-clinical-transplantation-liver
#3
Björn Nashan
The evidence base concerning use of mammalian target of rapamycin (mTOR) inhibitor therapy after liver transplantation is evolving rapidly, clarifying their benefits and disadvantages in different clinical scenarios. The H2304 trial showed that starting everolimus at 1 month posttransplant, with reduced tacrolimus, achieves a sustained improvement in renal function versus standard tacrolimus-based therapy, with at least equivalent immunosuppressive efficacy. Randomized studies evaluating early discontinuation of CNI therapy after introduction of an mTOR inhibitor consistently demonstrated a substantial improvement in renal function versus standard CNI therapy...
February 23, 2017: Transplantation
https://www.readbyqxmd.com/read/28230638/mtor-inhibition-cardiovascular-diseases-dyslipidemia-and-atherosclerosis
#4
Ammar Kurdi, Wim Martinet, Guido R Y De Meyer
Inhibitors of the mechanistic target of rapamycin (mTOR) have unique anti-atherosclerotic effects such as depletion of plaque macrophages, induction of autophagy and activation of cholesterol efflux. However, a common side effect of their use is dyslipidemia, a well-known risk factor for atherosclerosis. Indeed, mTOR inhibitors prevent lipid storage, increase LDL cholesterol levels and activate lipolysis. Although the net effect of mTOR inhibition seems favorable, the use of cholesterol lowering drugs to manage dyslipidemia remains the most recommended strategy...
February 23, 2017: Transplantation
https://www.readbyqxmd.com/read/28230637/mtor-inhibition-and-cardiovascular-diseases-cardiac-hypertrophy
#5
Ernesto Paoletti
Left ventricular hypertrophy (LVH) is highly prevalent in kidney transplant recipients, and is associated with poor clinical outcome. Immunosuppressive agents might affect LVH behavior after kidney transplantation. This review is an appraisal of available data regarding LVH in renal transplantation and especially of studies that evaluated LVH response to treatment. In particular, the role of mammalian target of rapamycin inhibitors adopted as immunosuppressive agents in kidney transplantation is reviewed in the light of recent studies that have shown LVH regression induced by this class of medications in kidney transplant recipients with posttransplant cardiomyopathy...
February 23, 2017: Transplantation
https://www.readbyqxmd.com/read/28230636/mtor-inhibition-clinical-transplantation-kidney
#6
Stuart M Flechner
No abstract text is available yet for this article.
February 23, 2017: Transplantation
https://www.readbyqxmd.com/read/28230361/10-gingerol-a-phytochemical-derivative-from-tongling-white-ginger-inhibits-cervical-cancer-insights-into-the-molecular-mechanism-and-inhibitory-targets
#7
Fang Zhang, Kiran Thakur, Fei Hu, Jian-Guo Zhang, Zhao-Jun Wei
With an aim to evaluate anti-cancerous activities of 10-gingerol (10-G) against Hela cells, it was purified and identified from Tongling White Ginger by HSCCC, UPLC-TOF-MS/MS and NMR analysis, respectively. 10-G inhibited the proliferation of HeLa cells at IC50 (29.19 μM) and IC80 (50.87 μM) with altered cell morphology, increased cytotoxicity and arrested cell cycle in G0/G1-phase. The most cell cycle related genes and proteins expression significantly decreased, followed by slight decrease in few and without affecting cyclin B1 and cyclin E1 (protein)...
February 23, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28229902/impact-of-high-glucose-and-ages-on-cultured-kidney-derived-cells-effects-on-cell-viability-lysosomal-enzymes-and-effectors-of-cell-signaling-pathways
#8
Giovani B Peres, Nestor Schor, Yara M Michelacci
We have previously reported decreased expression and activities of lysosomal cathepsins B and L in diabetic kidney. Relevant morphological changes were observed in proximal tubules, suggesting that these cells are implicated in the early stages of the disease. The aim of the present study was to investigate the mechanisms that lead to these changes. The effects of high glucose (HG) and advanced glycation end products (AGEs) on cell viability, lysosomal enzymes and other effectors of cell signaling of cultured kidney cells were studied...
February 13, 2017: Biochimie
https://www.readbyqxmd.com/read/28229367/inhibition-of-mtor-pathway-by-rapamycin-decreases-p-glycoprotein-expression-and-spontaneous-seizures-in-pharmacoresistant-epilepsy
#9
Xiaosa Chi, Cheng Huang, Rui Li, Wei Wang, Mengqian Wu, Jinmei Li, Dong Zhou
The mammalian target of rapamycin (mTOR) has been demonstrated to mediate multidrug resistance in various tumors by inducing P-glycoprotein (P-gp) overexpression. Here, we investigated the correlation between the mTOR pathway and P-gp expression in pharmacoresistant epilepsy. Temporal cortex specimens were obtained from patients with refractory mesial temporal lobe epilepsy (mTLE) and age-matched controls who underwent surgeries at West China Hospital of Sichuan University between June 2014 and May 2015. We established a rat model of epilepsy kindled by coriaria lactone (CL) and screened pharmacoresistant rats (non-responders) using phenytoin...
February 22, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28228357/activation-of-mtor-i%C3%AE%C2%BAb-%C3%AE-nf-%C3%AE%C2%BAb-pathway-contributes-to-lps-induced-hypotension-and-inflammation-in-rats
#10
Meryem Temiz-Resitoglu, Sefika Pinar Kucukkavruk, Demet Sinem Guden, Pelin Cecen, Ayse Nihal Sari, Bahar Tunctan, Aysegul Gorur, Lulufer Tamer-Gumus, Cuneyt Kemal Buharalioglu, Kafait U Malik, Seyhan Sahan-Firat
Mammalian target of rapamycin (mTOR), a serine/threonine kinase plays an important role in various pathophysiological processes including cancer, metabolic diseases, and inflammation. Although mTOR participates in Toll-like receptor 4 signalling in different cell types, the role of this enzyme in sepsis pathogenesis and its effects on hypotension and inflammation in endotoxemic rats remains unclear. In this study we investigated the effects of mTOR inhibition on lipopolysaccharide (LPS)-induced changes on expressions and/or activities of ribosomal protein S6 (rpS6), an mTOR substrate, nuclear factor-κB (NF-κB) p65, inhibitor κB (IκB)-α, inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2 with production of nitric oxide, peroxynitrite, prostacyclin, and tumor necrosis factor (TNF)-α and activity of myeloperoxidase (MPO), which results in hypotension and inflammation...
February 19, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28223693/single-cd28-stimulation-induces-stable-and-polyclonal-expansion-of-human-regulatory-t-cells
#11
Xuehui He, Ruben L Smeets, Esther van Rijssen, Annemieke M H Boots, Irma Joosten, Hans J P M Koenen
CD4+FOXP3+ Treg are essential for immune tolerance. Phase-1 clinical trials of Treg-therapy to treat graft-versus-host-disease reported safety and potential therapeutic efficacy. Treg-based trials have started in organ-transplant patients. However, efficient ex vivo expansion of a stable Treg population remains a challenge and exploring novel ways for Treg expansion is a pre-requisite for successful immunotherapy. Based on the recent finding that CD28-signaling is crucial for survival and proliferation of mouse Treg, we studied single-CD28 stimulation of human Treg, without T cell receptor stimulation...
February 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28223542/the-in-vitro-and-vivo-effects-of-nuclear-and-cytosolic-parafibromin-expression-on-the-aggressive-phenotypes-of-colorectal-cancer-cells-a-search-of-potential-gene-therapy-target
#12
Hua-Chuan Zheng, Jia-Jie Liu, Jing Li, Ji-Cheng Wu, Lei Yang, Gui-Feng Zhao, Xin Zhao, Hua-Mao Jiang, Ke-Qiang Huang, Zhi-Jie Li
Down-regulated parafibromin is positively linked to the pathogenesis of parathyroid, lung, breast, ovarian, gastric and colorectal cancers. Here, we found that wild-type (WT) parafibromin overexpression suppressed proliferation, tumor growth, induced cell cycle arrest and apoptosis in colorectal cancer cells (p<0.05), but it was the converse for mutant-type (MT, mutation in nucleus localization sequence) parafibromin (p<0.05). Both WT and MT transfectants inhibited migration and invasion, and caused better differentiation (p<0...
February 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28222438/microrna-29b-inhibits-angiogenesis-by-targeting-vegfa-through-the-mapk-erk-and-pi3k-akt-signaling-pathways-in-endometrial-carcinoma
#13
Hong-Xia Chen, Xiao-Xia Xu, Bu-Zhen Tan, Zhi Zhang, Xiao-Dong Zhou
OBJECTIVE: The purpose of this study is to explore the effects of microRNA-29b (miR-29b) regulating MAPK/ERK and PI3K/Akt signaling pathways on angiogenesis in endometrial carcinoma (EC) by targeting VEGFA. METHODS: Between February 2013 and April 2015, 126 EC patients admitted to the Second Affiliated Hospital of Nanchang University were randomly selected, with 126 EC tissues and the corresponding adjacent normal tissues collected after surgery. The human EC cell lines RL-95-2 and HEC-1-B and human endometrial cells were assigned to the normal group (human endometrial cells), the blank group (untransfected RL-95-2 or HEC-1-B cells), the pMIR-control group (RL-95-2 or HEC-1-B cells transfected with an empty vector), the pMIR-miR-29b group (RL-95-2 or HEC-1-B cells transfected with the miR-29b plasmid), LNA-control group (RL-95-2 or HEC-1-B cells transfected with an oligonucleotide inhibitors control), the LNA-miR-29b inhibitors group (RL-95-2 or HEC-1-B cells transfected with miRCURY LNATM miR-29b inhibitors), the LNA-miR-29b inhibitors + PD98059 group (RL-95-2 or HEC-1-B cells transfected with miRCURY LNATM miR-29b inhibitors and PD98059, an inhibitor of the MAPK/ERK signaling pathway) and the LNA-miR-29b inhibitors + wortmannin group (RL-95-2 or HEC-1-B cells transfected with miRCURY LNATM miR-29b inhibitors and wortmannin, an inhibitor of the PI3K/Akt signaling pathway)...
February 20, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28220839/pten-status-is-a-crucial-determinant-of-the-functional-outcome-of-combined-mek-and-mtor-inhibition-in-cancer
#14
Michele Milella, Italia Falcone, Fabiana Conciatori, Silvia Matteoni, Andrea Sacconi, Teresa De Luca, Chiara Bazzichetto, Vincenzo Corbo, Michele Simbolo, Isabella Sperduti, Antonina Benfante, Anais Del Curatolo, Ursula Cesta Incani, Federico Malusa, Adriana Eramo, Giovanni Sette, Aldo Scarpa, Marina Konopleva, Michael Andreeff, James Andrew McCubrey, Giovanni Blandino, Matilde Todaro, Giorgio Stassi, Ruggero De Maria, Francesco Cognetti, Donatella Del Bufalo, Ludovica Ciuffreda
Combined MAPK/PI3K pathway inhibition represents an attractive, albeit toxic, therapeutic strategy in oncology. Since PTEN lies at the intersection of these two pathways, we investigated whether PTEN status determines the functional response to combined pathway inhibition. PTEN (gene, mRNA, and protein) status was extensively characterized in a panel of cancer cell lines and combined MEK/mTOR inhibition displayed highly synergistic pharmacologic interactions almost exclusively in PTEN-loss models. Genetic manipulation of PTEN status confirmed a mechanistic role for PTEN in determining the functional outcome of combined pathway blockade...
February 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28219700/inhibition-of-ros-production-autophagy-or-apoptosis-signaling-reversed-the-anticancer-properties-of-antrodia-salmonea-in-triple-negative-breast-cancer-mda-mb-231-cells
#15
Chia-Ting Chang, Mallikarjuna Korivi, Hui-Chi Huang, Varadharajan Thiyagarajan, Kai-Yuan Lin, Pei-Jane Huang, Jer-Yuh Liu, You-Cheng Hseu, Hsin-Ling Yang
We investigated the in vitro and in vivo anticancer properties of Antrodia salmonea (AS), a well-known edible/medicinal mushroom in Taiwan, on human triple-negative breast cancer (MDA-MB-231) cells and xenografted nude mice; and revealed the underlying molecular mechanisms involved in autophagic- and apoptotic-cell death. Treatment of MDA-MB-231 cells with fermented culture broth of AS (0-200 μg/mL) inhibited cell viability/growth. AS-induced autophagy was evidenced via increased LC3-II accumulation, GFP-LC3 puncta and AVOs formation in MDA-MB-231 cells...
February 17, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28219050/synergism-and-mechanism-of-astragaloside-iv-combined-with-ginsenoside-rg1-against-autophagic-injury-of-pc12-cells-induced-by-oxygen-glucose-deprivation-reoxygenation
#16
Xiao-Ping Huang, Huang Ding, Xiao-Qian Yang, Jing-Xian Li, Biao Tang, Xiao-Dan Liu, Ying-Hong Tang, Chang-Qing Deng
The aim of this study was to explore the effect by which the combination of Astragaloside IV (AST IV) and Ginsenoside Rg1 (Rg1) resisted autophagic injury in PC12 cells induced by oxygen glucose deprivation/reoxygenation (OGD/R). We studied the nature of the interaction between AST IV and Rg1 that inhibited autophagy through the Isobologram method, and investigated the synergistic mechanism via the PI3K I/Akt/mTOR and PI3K III/Becline-1/Bcl-2 signaling pathways. Our results showed that, based on the 50% inhibiting concentration (IC50), AST IV combined with Rg1 at a 1:1 ratio resulted in a synergistic effect, whereas the combination of the two had an antagonistic effect on autophagy at ratios of 1:2 and 2:1...
February 17, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28216662/ddx5-promotes-gastric-cancer-cell-proliferation-in-vitro-and-in-vivo-through-mtor-signaling-pathway
#17
Cheng Du, Dan-Qi Li, Na Li, Li Chen, Shi-Sen Li, Yang Yang, Ming-Xiao Hou, Man-Jiang Xie, Zhen-Dong Zheng
DEAD (Asp-Glu-Ala-Asp) box helicase 5 (DDX5) is an ATP-dependent RNA helicase that is overexpressed in various malignancies. Increasing evidence suggests that DDX5 participates in carcinogenesis and cancer progression via promoting cell proliferation and metastasis. However, the functional role of DDX5 in gastric cancer is largely unknown. In this study, we observed that DDX5 was significantly up-regulated in gastric cancer tissues compared with the paired adjacent normal tissues. The expression of DDX5 correlated strongly with Ki67 index and pathological stage of gastric cancer...
February 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28216154/the-effect-of-indatraline-on-angiogenesis-suppression-through-hif-1%C3%AE-mediated-vegf-inhibition
#18
Chih-Na Yen, Yoon Sun Cho, Ho Jeong Kwon
The present research reports a novel biological activity of indatraline, a compound clinically used as an antidepressant. We previously identified indatraline as an autophagy inducer. Autophagy is an intracellular catabolic pathway for degrading or recycling unnecessary organelles in response to cellular stress. Indatraline-mediated autophagy induction results from mTOR inhibition. The mTOR is a negative regulator of autophagy as well as a master regulator of angiogenesis. Angiogenesis defines the process by which new vessels are formed from pre-existing vascular tissues, providing nutrients to cancer cells, allowing rapid tumor progression...
February 17, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28216152/1-25-dihydroxyvitamin-d3-prevents-the-development-of-diabetic-cardiomyopathy-in-type-1-diabetic-rats-by-enhancing-autophagy-via-inhibiting-the-%C3%AE-catenin-tcf4-gsk-3%C3%AE-mtor-pathway
#19
Huili Wei, Hua Qu, Hang Wang, Baolan Ji, Yao Ding, Dan Liu, Yang Duan, Huimin Liang, Chuan Peng, Xiaoqiu Xiao, Huacong Deng
Diabetic cardiomyopathy (DCM) can increase the risk of heart failure and death in diabetic patients. However, no effective approaches are available to prevent its progression and development. Studies have shown that vitamin D is greatly implicated in cardiac hypertrophy and fibrosis, and there is a high prevalence of vitamin D deficiency in diabetic patients. In this study, we investigated whether 1,25-Dihydroxyvitamin-D3 (1,25D3) can improve DCM through a vitamin D receptor (VDR)-dependent mechanism associated with autophagy and the β-catenin/T-cell factor/lymphoid enhancer factor (TCF4)/glycogen synthase kinase-3β (GSK-3β)/mammalian target of rapamycin (mTOR) pathway...
February 17, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28214861/sirt1-regulates-the-inflammatory-response-of-vascular-adventitial-fibroblasts-through-autophagy-and-related-signaling-pathway
#20
Wei-Rong Wang, Ting-Ting Li, Ting Jing, Yan-Xiang Li, Xiao-Feng Yang, Yan-Hao He, Wei Zhang, Rong Lin, Ji-Ye Zhang
BACKGROUND/AIMS: Autophagy is a lysosomal degradation pathway that is essential for cellular survival, differentiation, and homeostasis. Sirtuin 1 (SIRT1), a NAD+-dependent deacetylase, plays a pivotal role in modulation of autophagy. Recent studies found that autophagy was involved in the regulation of inflammatory response. In this study, we aimed to determine the effect of SIRT1 on autophagy and inflammation, and whether autophagy can regulate the inflammatory response in vascular adventitial fibroblasts (VAFs)...
February 3, 2017: Cellular Physiology and Biochemistry
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