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Rapamycin

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https://www.readbyqxmd.com/read/29906337/retained-differentiation-capacity-of-human-skeletal-muscle-satellite-cells-from-spinal-cord-injured-individuals
#1
Mladen Savikj, Maxwell A Ruby, Emil Kostovski, Per O Iversen, Juleen R Zierath, Anna Krook, Ulrika Widegren
Despite the well-known role of satellite cells in skeletal muscle plasticity, the effect of spinal cord injury on their function in humans remains unknown. We determined whether spinal cord injury affects the intrinsic ability of satellite cells to differentiate and produce metabolically healthy myotubes. We obtained vastus lateralis biopsies from eight spinal cord-injured and six able-bodied individuals. Satellite cells were isolated, grown and differentiated in vitro. Gene expression was measured by quantitative PCR...
June 2018: Physiological Reports
https://www.readbyqxmd.com/read/29905853/2-methoxyestradiol-inhibits-hypoxia-induced-scleroderma-fibroblast-collagen-synthesis-by-phosphatidylinositol-3-kinase-akt-mtor-signalling
#2
Xing Zhou, Chaofan Liu, Jinghao Lu, Lubing Zhu, Ming Li
Objectives: To investigate the mechanism of 2-methoxyestradiol (2-ME) in inhibiting hypoxia-induced collagen synthesis of fibroblasts in SSc. Methods: The expressions of hypoxia-inducible factor 1 alpha (HIF-1α) and connective tissue growth factor (CTGF) in skin specimens derived from SSc patients and healthy volunteers were examined by immunohistochemistry. HIF-1α was knocked down by lentiviral transduction, and SSc dermal fibroblasts cultured under normoxic (21% O2) or hypoxic (1% O2) condition were treated with PI3K inhibitor LY294002, rapamycin or 2-ME (25 μM)...
June 13, 2018: Rheumatology
https://www.readbyqxmd.com/read/29904919/linc00968-functions-as-an-oncogene-in-osteosarcoma-by-activating-the-pi3k-akt-mtor-signaling
#3
Gang Liu, Dongtang Yuan, Peng Sun, Weidong Liu, Peng-Fei Wu, Huan Liu, Guang-Yang Yu
Osteosarcoma is recognized as a malignant tumor in the skeletal system. Long non-coding RNAs (lncRNAs) have been exhibited to play crucial roles in osteosarcoma development. Our current study focused on the biological effects and mechanism of LINC00968 in osteosarcoma pathogenesis. We observed that LINC00968 was dramatically elevated in osteosarcoma cells including U2OS, MG63, Saos-2, SW1353, and 143-B cells compared to human osteoblast cell line hFOB. Silence of LINC00968 inhibited osteosarcoma cell growth and proliferation in vitro...
June 15, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29904395/rapamycin-provides-anti-epileptogenic-effect-in-a-rat-model-of-post-traumatic-epilepsy-via-deactivation-of-mtor-signaling-pathway
#4
Feng Wang, Fuxiang Chen, Genbo Wang, Shushan Wei, Fu Fang, Dezhi Kang, Yuanxiang Lin
The mammalian target of rapamycin (mTOR) signaling pathway has attracted much attention in recent years. However, the contribution of mTOR activation to the development of post-traumatic epilepsy (PTE) remains largely unknown. The purpose of the present study was to investigate the activation of mTOR signaling in a rat model of FeCl2 -induced PTE, and to explore the potential effect of its specific inhibitor rapamycin. The results indicated that the expression levels of p-mTOR and p-P70S6K, the overactivation biomarkers of mTOR signaling, increased significantly in hippocampal and perilesional cortex following PTE induction...
June 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29902763/synergistic-effect-of-rapamycin-and-metformin-against-germ-cell-apoptosis-and-oxidative-stress-after-testicular-torsion-detorsion-induced-ischemia-reperfusion-in-rats
#5
Morteza Ghasemnejad-Berenji, Mahmoud Ghazi-Khansari, Sarvin Pashapour, Abbas Jafari, Iraj Yazdani, Hojjat Ghasemnejad-Berenji, Seyed Soheil Saeedi Saravi, Sonia Sadeghpour, Maliheh Nobakht, Alireza Abdollahi, Javad Mohajer Ansari, Ahmad Reza Dehpour
The aim of this study was to investigate the effects of rapamycin (rapa) and metformin (met), combined administration on testicular torsion-detorsion (T/D) injury. A total of 108 male rats were divided randomly into six groups (n = 18), control, sham-operated, T/D, T/D + met (100 mg/kg), T/D + rapa (0.25 mg/kg) and T/D + met (100 mg/kg)+rapa (0.25 mg/kg). Except for the control and sham groups, torsion was created by rotating the right testis 720° in a clockwise direction for 1 h...
June 11, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29901635/rapamycin-treatment-for-amyotrophic-lateral-sclerosis-protocol-for-a-phase-ii-randomized-double-blind-placebo-controlled-multicenter-clinical-trial-rap-als-trial
#6
Jessica Mandrioli, Roberto D'Amico, Elisabetta Zucchi, Annalisa Gessani, Nicola Fini, Antonio Fasano, Claudia Caponnetto, Adriano Chiò, Eleonora Dalla Bella, Christian Lunetta, Letizia Mazzini, Kalliopi Marinou, Gianni Sorarù, Sara de Biasi, Domenico Lo Tartaro, Marcello Pinti, Andrea Cossarizza
INTRODUCTION: Misfolded aggregated proteins and neuroinflammation significantly contribute to amyotrophic lateral sclerosis (ALS) pathogenesis, hence representing therapeutic targets to modify disease expression. Rapamycin inhibits mechanistic target of Rapamycin (mTOR) pathway and enhances autophagy with demonstrated beneficial effects in neurodegeneration in cell line and animal models, improving phenotype in SQSTM1 zebrafish, in Drosophila model of ALS-TDP, and in the TDP43 mouse model, in which it reduced neuronal loss and TDP43 inclusions...
June 2018: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29901441/optical-coherence-tomography-substudy-of-a-prospective-multicenter-randomized-post-market-trial-to-assess-the-safety-and-effectiveness-of-the-firehawk%C3%A2-rapamycin-target-eluting-cobalt-chromium-coronary-stent-system-for-the-treatment-of-atherosclerotic-lesions
#7
Andreas Baumbach, Alexandra J Lansky, Yoshi Onuma, Taku Asano, Thomas Johnson, Richard Anderson, Ferdinand Kiemeneij, Ming Zheng, Niels Van Royen, Ton Slagboom, Georg Vlachojannis, Bo Xu, Patrick Serruys, William Wijns
AIMS: Durable polymer drug-eluting stents (DP DES) may contribute to persistent inflammation, delayed endothelial healing and subsequent late DES thrombosis. The aim of this Optical Coherence Tomography (OCT) sub-study was to compare healing and neointimal coverage of a novel bioabsorbable polymer sirolimus-eluting stent (FIREHAWK®) (BP DES) versus the DP DES (XIENCE) at 90 days in an all comers patient population. METHODS AND RESULTS: The TARGET All Comers study is a prospective multicenter randomised post-market trial of 1656 patients randomised 1:1 to FIREHAWK or XIENCE at 21 centers in 10 European countries...
June 12, 2018: EuroIntervention
https://www.readbyqxmd.com/read/29901118/the-effect-of-mg%C3%A2-2zn%C3%A2-0-5nd-alloy-on-the-mtor-signalling-pathway-in-l6-cells
#8
Wei Lu, Lei Guo, Tianlong Jiang, Shenghui Ni, Yuyan Zhao
Magnesium alloys have shown potential as biodegradable metallic materials for orthopaedic applications due to their degradability, and their resemblance to cortical bone and biocompatible degradation/corrosion products. However, the fast corrosion rate and the potential toxicity of their alloying element has limited the clinical application of Mg alloys. In the present study, a novel Mg‑2Zn‑0.5Nd alloy was prepared, and then the effects on the cell biological behaviour of the Mg‑2Zn‑0.5Nd alloy was compared with 317L stainless steel and titanium (Ti‑6Al‑4V) alloys as controls...
May 30, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29901111/dihydrocelastrol-exerts-potent-antitumor-activity-in-mantle-cell-lymphoma-cells-via-dual-inhibition-of-mtorc1-and-mtorc2
#9
Yongsheng Xie, Bo Li, Wenxuan Bu, Lu Gao, Yong Zhang, Xiucai Lan, Jun Hou, Zhijian Xu, Shuaikang Chang, Dandan Yu, Bingqian Xie, Yingcong Wang, Houcai Wang, Yiwen Zhang, Xiaosong Wu, Weiliang Zhu, Jumei Shi
Mantle cell lymphoma (MCL) is a distinct and highly aggressive subtype of B-cell non-Hodgkin lymphoma. Dihydrocelastrol (DHCE) is a dihydro-analog of celastrol, which is isolated from the traditional Chinese medicinal plant Tripterygium wilfordii. The present study aimed to investigate the effects of DHCE treatment on MCL cells, and to determine the mechanism underlying its potent antitumor activity in vitro and in vivo using the Cell Counting kit-8 assay, clonogenic assay, apoptosis assay, cell cycle analysis, immunofluorescence staining, western blotting and tumor xenograft models...
June 12, 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29901107/autophagy-protects-bone-marrow-mesenchymal-stem-cells-from-palmitate%C3%A2-induced-apoptosis-through-the-ros%C3%A2-jnk-p38-mapk-signaling-pathways
#10
Yongyi Liu, Ning Wang, Shaokun Zhang, Qingwei Liang
In recent years, the association between saturated fatty acids (FA) and bone cells has received a high level of attention. Previous studies have shown that palmitate (PA), a common saturated FA, can cause apoptosis in bone marrow mesenchymal stem cells (BMSCs). However, whether PA can induce autophagy, an important intracellular protection mechanism that is closely associated with apoptosis, in BMSCs is still unknown; the association between autophagy and apoptosis is also unclear. The aim of the present study was to determine whether PA can induce autophagy in BMSCs...
May 30, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29901097/microrna%C3%A2-155-contributes-to-the-occurrence-of-epilepsy-through-the-pi3k-akt-mtor-signaling-pathway
#11
Wei Duan, Yan Chen, Xiao-Rong Wang
Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to measure the expression of microRNA-155 in patients with temporal lobe epilepsy. Commercial kit and western blot analysis were used to measure gap-associated protein expression. The aim of the present study was to investigate the effect of microRNA‑155 (miRNA‑155) in the occurrence of epilepsy and the molecular mechanism involved. In patients with temporal lobe epilepsy, miRNA‑155 expression was evidently higher than that in patients of the normal volunteers group...
June 1, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29901092/efficacy-prediction-of-targeted-therapy-for-gastric-cancer-the-current-status-review
#12
Wanjing Feng, Xiaodong Zhu
Despite significant progress in the treatment of gastric cancer (GC), the prognosis remains poor and the mortality is high. Targeted drugs have been incorporated into routine treatment to improve treatment efficacy. However, the therapy response is still below 50%. Therefore, there is a need to identify predictive factors for patient response to a specific drug in order to improve the efficacy of drug therapy. The present article reviewed the predictive factors for target therapy in GC, including epidermal growth factor receptor, human epidermal receptor 2, vascular endothelial growth factor family, molecules in the mesenchymal‑epithelial transition pathway and the mammalian target of rapamycin...
June 6, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29899972/ketamine-and-rapid-acting-antidepressants-a-new-era-in-the-battle-against-depression-and-suicide
#13
REVIEW
Ronald S Duman
Therapeutic medications for the treatment of depression have serious limitations, particularly delayed onset and low rates of efficacy. However, the discovery that a single subanesthetic dose of ketamine, a glutamate NMDA receptor channel blocker, can produce a rapid (within hours) antidepressant response that is sustained (about 1 week), even in patients considered treatment-resistant, has invigorated the field. In addition to these remarkable actions, ketamine has proven effective for the treatment of suicidal ideation...
2018: F1000Research
https://www.readbyqxmd.com/read/29899823/metformin-exerts-antitumor-activity-via-induction-of-multiple-death-pathways-in-tumor-cells-and-activation-of-a-protective-immune-response
#14
Felipe V Pereira, Amanda Campelo L Melo, Jun Siong Low, Íris Arantes de Castro, Tárcio T Braga, Danilo C Almeida, Ana Gabriela U Batista de Lima, Meire I Hiyane, Matheus Correa-Costa, Vinicius Andrade-Oliveira, Clarice S T Origassa, Rosana M Pereira, Susan M Kaech, Elaine G Rodrigues, Niels Olsen S Câmara
The antitumor effect of metformin has been demonstrated in several types of cancer; however, the mechanisms involved are incompletely understood. In this study, we showed that metformin acts directly on melanoma cells as well as on the tumor microenvironment, particularly in the context of the immune response. In vitro , metformin induces a complex interplay between apoptosis and autophagy in melanoma cells. The anti-metastatic activity of metformin in vivo was assessed in several mouse models challenged with B16F10 cells...
May 25, 2018: Oncotarget
https://www.readbyqxmd.com/read/29899208/chrysin-attenuates-cell-viability-of-human-colorectal-cancer-cells-through-autophagy-induction-unlike-5-fluorouracil-oxaliplatin
#15
Yueh-Ming Lin, Chih-I Chen, Yi-Ping Hsiang, Yung-Chia Hsu, Kung-Chuan Cheng, Pei-Hsuan Chien, Hsiao-Lin Pan, Chien-Chang Lu, Yun-Ju Chen
Chemotherapeutic 5-fluorouracil (5-FU) combined with oxaliplatin is often used as the standard treatment for colorectal cancer (CRC). The disturbing side effects and drug resistance commonly observed in chemotherapy motivate us to develop alternative optimal therapeutic options for CRC treatment. Chrysin, a natural and biologically active flavonoid abundant in propolis, is reported to have antitumor effects on a few CRCs. However, whether and how chrysin achieves similar effectiveness to the 5-FU combination is not clear...
June 14, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29899101/porcine-reproductive-and-respiratory-syndrome-virus-infection-induces-both-eif2%C3%AE-phosphorylation-dependent-and-independent-host-translation-shutoff
#16
Yang Li, Liurong Fang, Yanrong Zhou, Ran Tao, Dang Wang, Shaobo Xiao
Porcine reproductive and respiratory syndrome virus (PRRSV) is an Arterivirus that has caused tremendous economic losses in the global swine industry since it was discovered in the late 1980s. Inducing host translation shutoff is a strategy used by many viruses to optimize their replication and spread. Here, we demonstrate that PRRSV infection causes host translation suppression, which is strongly dependent on viral replication. By screening PRRSV-encoded nonstructural proteins (nsps), we found that nsp2 participates in the induction of host translation shutoff and that its transmembrane (TM) domain is required for this process...
June 13, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29898984/kinome-expansion-in-the-fusarium-oxysporum-species-complex-driven-by-accessory-chromosomes
#17
Gregory A DeIulio, Li Guo, Yong Zhang, Jonathan M Goldberg, H Corby Kistler, Li-Jun Ma
The Fusarium oxysporum species complex (FOSC) is a group of soilborne pathogens causing severe disease in more than 100 plant hosts, while individual strains exhibit strong host specificity. Both chromosome transfer and comparative genomics experiments have demonstrated that lineage-specific (LS) chromosomes contribute to the host-specific pathogenicity. However, little is known about the functional importance of genes encoded in these LS chromosomes. Focusing on signaling transduction, this study compared the kinomes of 12 F...
June 27, 2018: MSphere
https://www.readbyqxmd.com/read/29898808/facile-analysis-of-protein-protein-interactions-in-living-cells-by-enriched-visualization-of-the-p-body
#18
Miri Choi, Jiyeon Baek, Sang-Bae Han, Sungchan Cho
Protein-Protein Interactions (PPIs) play essential roles in diverse biological processes and their misregulations are associated with a wide range of diseases. Especially, the growing attention to PPIs as a new class of therapeutic target is increasing the need for an efficient method of cell-based PPI analysis. Thus, we newly developed a robust PPI assay (SeePPI) based on the co-translocation of interacting proteins to the discrete subcellular compartment 'processing body' (p-body) inside living cells, enabling a facile analysis of PPI by the enriched fluorescent signal...
June 14, 2018: BMB Reports
https://www.readbyqxmd.com/read/29898734/knockdown-of-klf5-suppresses-hypoxia-induced-resistance-to-cisplatin-in-nsclc-cells-by-regulating-hif-1%C3%AE-dependent-glycolysis-through-inactivation-of-the-pi3k-akt-mtor-pathway
#19
Tianxiao Gong, Liuqing Cui, Haili Wang, Haoxun Wang, Na Han
BACKGROUND: Hypoxia-mediated chemoresistance has been regarded as an important obstacle in the development of cancer treatment. Knockdown of krüppel-like factor 5 (KLF5) was reported to inhibit hypoxia-induced cell survival and promote cell apoptosis in non-small cell lung cancer (NSCLC) cells via direct regulation of hypoxia inducible factor-1α (HIF-1α) expression. However, the roles of KLF5 in the development of hypoxia-induced cisplatin (DDP) resistance and its underlying mechanism in NSCLC cells remain to be further elucidated...
June 14, 2018: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29898430/mir-338-modulates-proliferation-and-autophagy-by-pi3k-akt-mtor-signaling-pathway-in-cervical-cancer
#20
Rong Lu, Zhanhua Yang, Guoying Xu, Shengsheng Yu
Cervical cancer (CC) is a malignant solid tumor, which is one of the main causes of morbidity and mortality in women. Given that autophagy is an important factor promoting tumor progression, we aim to investigate the functional role of miR-338 in autophagy and proliferation of cervical cancer. In our study, expression of miR-338 was validated by quantitative RT-PCR in 30 paired cervical cancer tissues and normal tissues. We performed MTT, colony formation and cell cycle assay to explore the effect of miR-338 on cell proliferation...
June 10, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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