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https://www.readbyqxmd.com/read/28984836/balanced-diet-fed-fat-1-transgenic-mice-exhibit-lower-hindlimb-suspension-induced-soleus-muscle-atrophy
#1
Gabriel Nasri Marzuca-Nassr, Gilson Masahiro Murata, Amanda Roque Martins, Kaio Fernando Vitzel, Amanda Rabello Crisma, Rosângela Pavan Torres, Jorge Mancini-Filho, Jing Xuan Kang, Rui Curi
The consequences of two-week hindlimb suspension (HS) on skeletal muscle atrophy were investigated in balanced diet-fed Fat-1 transgenic and C57BL/6 wild-type mice. Body composition and gastrocnemius fatty acid composition were measured. Skeletal muscle force, cross-sectional area (CSA), and signaling pathways associated with protein synthesis (protein kinase B, Akt; ribosomal protein S6, S6, eukaryotic translation initiation factor 4E-binding protein 1, 4EBP1; glycogen synthase kinase3-beta, GSK3-beta; and extracellular-signal-regulated kinases 1/2, ERK 1/2) and protein degradation (atrophy gene-1/muscle atrophy F-box, atrogin-1/MAFbx and muscle RING finger 1, MuRF1) were evaluated in the soleus muscle...
October 6, 2017: Nutrients
https://www.readbyqxmd.com/read/28965934/the-activation-of-autophagy-protects-neurons-and-astrocytes-against-bilirubin-induced-cytotoxicity
#2
Mohammed Qaisiya, Paula Mardešić, Beatrice Pastore, Claudio Tiribelli, Cristina Bellarosa
Unconjugated bilirubin (UCB) neurotoxicity involves oxidative stress, calcium signaling and ER-stress. The same insults can also induce autophagy, a process of "self-eating", with both a pro-survival or a pro-apoptotic role. Our aim was to study the outcome of autophagy activation by UCB in the highly sensitive neuronal SH-SY5Y cells and in the resistant astrocytoma U87 cells. Upon treatment with a toxic dose of UCB, the conversion of LC3-I to LC3-II was detected in both cell lines. Inhibition of autophagy by E64d before UCB treatment increased SH-SY5Y cell mortality and made U87 cells sensitive to UCB...
September 28, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28962554/propofol-enhances-bcr-abl-tkis-inhibitory-effects-in-chronic-myeloid-leukemia-through-akt-mtor-suppression
#3
Zhimin Tan, Aixia Peng, Jingwen Xu, Mingwen Ouyang
BACKGROUND: The anti-cancer activities of intravenous anesthetic drug propofol have been demonstrated in various types of cancers but not in chronic myeloid leukemia (CML). METHODS: We systematically examined the effect of propofol and its combination with BCR-ABL tyrosine kinase inhibitors (TKIs) in CML cell lines, patient progenitor cells and mouse xenograft model. We analyzed propofol's underlying mechanism focusing on survival pathway in CML cells. RESULTS: We show that propofol alone is active in inhibiting proliferation and inducing apoptosis in KBM-7, KU812 and K562 cells, and acts synergistically with imatinib or dasatinib, in in vitro cell culture system and in vivo xenograft model...
September 29, 2017: BMC Anesthesiology
https://www.readbyqxmd.com/read/28961193/fascaplysin-exerts-anti-cancer-effects-through-the-downregulation-of-survivin-and-hif-1%C3%AE-and-inhibition-of-vegfr2-and-trka
#4
Taek-In Oh, Yoon-Mi Lee, Taek-Jin Nam, Young-San Ko, Shinmee Mah, Jinhee Kim, Younghoon Kim, Rallabandi Harikrishna Reddy, Young Jun Kim, Sungwoo Hong, Ji-Hong Lim
Fascaplysin has been reported to exert anti-cancer effects by inhibiting cyclin-dependent kinase 4 (CDK4); however, the precise mode of action by which fascaplysin suppresses tumor growth is not clear. Here, we found that fascaplysin has stronger anti-cancer effects than other CDK4 inhibitors, including PD0332991 and LY2835219, on lung cancer cells that are wild-type or null for retinoblastoma (RB), indicating that unknown target molecules might be involved in the inhibition of tumor growth by fascaplysin. Fascaplysin treatment significantly decreased tumor angiogenesis and increased cleaved-caspase-3 in xenografted tumor tissues...
September 29, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28939765/thioredoxin-1-maintains-mtor-function-during-oxidative-stress-in-cardiomyocytes
#5
Shin-Ichi Oka, Tsuyoshi Hirata, Wataru Suzuki, Daichi Naito, Yanbin Chen, Adave Chin, Hiroaki Yaginuma, Toshiro Saito, Narayani Nagarajan, Peiyong Zhai, Santosh Bhat, Kevin Schesing, Dan Shao, Yoko Hirabayashi, Junji Yodoi, Sebastiano Sciarretta, Junichi Sadoshima
Thioredoxin 1 (Trx1) is a 12 kDa oxidoreductase that catalyzes thiol-disulfide exchange reactions to reduce proteins with disulfide bonds. As such, Trx1 helps protect the heart against stresses, such as ischemia and pressure overload. Mechanistic target of rapamycin (mTOR) is a serine/threonine kinase that regulates cell growth, metabolism and survival. We have previously shown that mTOR activity is increased in response to myocardial ischemia-reperfusion injury. However, whether Trx1 interacts with mTOR to preserve heart function remains unknown...
September 22, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28927274/fluoride-induced-autophagy-via-the-regulation-of-phosphorylation-of-mammalian-targets-of-rapamycin-in-mice-leydig-cells
#6
Jianhai Zhang, Yuchen Zhu, Yan Shi, Yongli Han, Chen Liang, Zhiyuan Feng, Heping Zheng, Michelle Eng, Jundong Wang
Fluoride is known to impair testicular function and decrease testosterone levels, yet the underlying mechanisms remain inconclusive. The objective of this study is to investigate the roles of autophagy in fluoride-induced male reproductive toxicity using both in vivo and in vitro Leydig cell models. Using transmission electron microscopy and monodansylcadaverine staining, we observed increasing numbers of autophagosomes in testicular tissue, especially in Leydig cells of fluoride-exposed mice. Further study revealed that fluoride increased the levels of mRNA and protein expression of autophagy markers LC3, Beclin1, and Atg 5 in primary Leydig cells...
October 11, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28919376/microrna-218-5p-as-a-potential-target-for-the-treatment-of-human-osteoarthritis
#7
Jun Lu, Ming-Liang Ji, Xue-Jun Zhang, Pei-Liang Shi, Hao Wu, Chen Wang, Hee-Jeong Im
Emerging evidence suggests that dysregulated microRNAs (miRNAs) play a pivotal role in osteoarthritis (OA), but the role of specific miRNAs remains unclear. Accordingly, we identified OA-associated miRNAs and functional validation of results. Here, we demonstrate that miR-218-5p is significantly upregulated in moderate and severe OA and correlates with scores on a modified Mankin scale. Through gain-of-function and loss-of-function studies, miR-218-5p was shown to significantly affect matrix synthesis gene expression and chondrocyte proliferation and apoptosis...
August 19, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28884839/effects-of-glut1-gene-silencing-on-proliferation-differentiation-and-apoptosis-of-colorectal-cancer-cells-by-targeting-the-tgf-%C3%AE-pi3k-akt-mtor-signaling-pathway
#8
Xue-Liang Wu, Li-Kun Wang, Dong-Dong Yang, Ming Qu, Yong-Jiang Yang, Fei Guo, Lei Han, Jun Xue
This study aims to investigate the effects of glucose transport l (Glut1) gene on proliferation, differentiation and apoptosis of colorectal cancer (CRC) cells by regulating the TGF-β/PI3K-AKT-mTOR signaling pathway. Immunohistochemistry was conducted to detect the positive Glut1 expression. Normal human CRC epithelial cells (CCD-18Co) and CRC cell line HCT116 were grouped into the control, blank, negative control (NC), and shGlut1-1 groups. RT-qPCR and Western blotting were performed to detect the expressions of Glut1, TGF-β1, PI3K, AKT, PTEN, mTOR, Bcl-2 and Bax...
September 8, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28879901/braf-gene-alterations-and-enhanced-mammalian-target-of-rapamycin-signaling-in-gangliogliomas
#9
Aanchal Kakkar, Atreye Majumdar, Pankaj Pathak, Anupam Kumar, Kalpana Kumari, Manjari Tripathi, Mehar C Sharma, Vaishali Suri, Vivek Tandon, Sarat P Chandra, Chitra Sarkar
BACKGROUND: Gangliogliomas (GGs) are slow-growing glioneuronal tumors seen in children and young adults. They are associated with intractable epilepsy, and have recently been found to harbor BRAF (B- rapidly accelerated fibrosarcoma) gene mutations. However, the mammalian target of rapamycin (mTOR) signaling pathway, downstream of BRAF, has not been evaluated extensively in GGs. MATERIALS AND METHODS: GG cases were retrieved, clinical data obtained, and histopathological features reviewed...
September 2017: Neurology India
https://www.readbyqxmd.com/read/28865848/grain-challenge-affects-systemic-and-hepatic-molecular-biomarkers-of-inflammation-stress-and-metabolic-responses-to-a-greater-extent-in-holstein-than-jersey-cows
#10
T Xu, F C Cardoso, A Pineda, E Trevisi, X Shen, F Rosa, J S Osorio, J J Loor
Long-term feeding of high-grain diets to dairy cows often results in systemic inflammation characterized by alterations in acute-phase proteins and other biomarkers, both in plasma and immune-responsive tissues like the liver. The molecular and systemic changes that characterize an acute grain feeding challenge remain unclear. The current study involved 6 Holstein and 6 Jersey cows in a replicated 2 × 2 Latin square. Periods (10 d) were divided into 4 stages (S): S1, d 1 to 3, served as baseline with total mixed ration (TMR) ad libitum; S2, d 4, served as restricted feeding, with cows offered 50% of the average daily intake observed in S1; S3, d 5, a grain challenge was performed, in which cows were fed a TMR ad libitum without (CON) or with an additional pellet wheat-barley (1:1; HIG) at 20% of dry matter intake top-dressed onto the TMR; S4, d 6 to 10, served as recovery during which cows were allowed ad libitum access to the TMR...
November 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28833404/suppression-of-c-myc-enhances-p21-waf1-cip1-mediated-g1-cell-cycle-arrest-through-the-modulation-of-erk-phosphorylation-by-ascochlorin
#11
Yun-Jeong Jeong, Hyang-Sook Hoe, Hyun-Ji Cho, Kwan-Kyu Park, Dae-Dong Kim, Cheorl-Ho Kim, Junji Magae, Dong Wook Kang, Sang-Rae Lee, Young-Chae Chang
Numerous anti-cancer agents inhibit cell cycle progression via a p53-dependent mechanism; however, other genes such as the proto-oncogene c-Myc are promising targets for anticancer therapy. In the present study, we provide evidence that ascochlorin, an isoprenoid antibiotic, is a non-toxic anti-cancer agent that induces G1 cell cycle arrest and p21(WAF1/CIP1) expression by downregulating of c-Myc protein expression. Ascochlorin promoted the G1 arrest, upregulated p53 and p21(WAF1/CIP1) , and downregulated c-Myc in HCT116 cells...
August 18, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28810331/-effect-of-tsc2-gene-expression-downregulation-by-lentivirus-induced-rna-interference-on-u937-cell-line-and-its-mechanism
#12
Z F Xu, H X Liu, Y H Tan, X H Chen, F G Ren, Y F Zhang, J M Chang, N Zhang, J J Hu, H W Wang
Objective: To investigate the effect of biology and mTOR pathway activity of down-regulated TSC2 gene expression on U937 leukemia cells. Methods: Gene expression was down-regulated by lentivirus induced RNA interference on TSC2 high expressed U937 cell line; the proliferation, apoptosis and differentiation were detected by CCK-8 assay, colony formation assay and flow cytometry; the gene expression level and protein kinase activity were detected by qRT-PCR and Western blot. Results: Down-regulated expression of TSC2 gene promoted U937 cell proliferation and colony formation ability (P<0...
July 14, 2017: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/28783736/glutamate-alleviates-muscle-protein-loss-by-modulating-tlr4-nods-akt-foxo-and-mtor-signaling-pathways-in-lps-challenged-piglets
#13
Ping Kang, Xiuying Wang, Huanting Wu, Huiling Zhu, Yongqing Hou, Longmei Wang, Yulan Liu
The experiment was conducted to study the effect of the glutamate (Glu) on muscle protein loss through toll-like receptor 4 (TLR4), nucleotide-binding oligomerization domain proteins (NODs), Akt/Forkhead Box O (Akt/FOXO) and mammalian target of rapamycin (mTOR) signaling pathways in LPS-challenged piglets. Twenty-four weaned piglets were assigned into four treatments: (1) Control; (2) LPS+0% Glu; (3) LPS + 1.0% Glu; (4) LPS + 2.0% Glu. The experiment was lasted for 28 days. On d 28, the piglets in the LPS challenged groups were injected with LPS on 100 μg/kg body weight (BW), and the piglets in the control group were injected with the same volume of 0...
2017: PloS One
https://www.readbyqxmd.com/read/28774796/synergistic-anti-tumor-effect-of-17aag-with-the-pi3k-mtor-inhibitor-nvp-bez235-on-human-melanoma
#14
R Calero, E Morchon, I Martinez-Argudo, R Serrano
Drug resistance by MAPK signaling recovery or activation of alternative signaling pathways, such as PI3K/AKT/mTOR, is an important factor that limits the long-term efficacy of targeted therapies in melanoma patients. In the present study, we investigated the phospho-proteomic profile of RTKs and its correlation with downstream signaling pathways in human melanoma. We found that tyrosine kinase receptors expression correlated with the expression of pivotal downstream components of the RAS/RAF/MAPK and PI3K/AKT/mTOR pathways in melanoma cell lines and tumors...
October 10, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28728363/effect-of-different-levels-of-protein-concentrates-supplementation-on-the-growth-performance-plasma-amino-acids-profile-and-mtor-cascade-genes-expression-in-early-weaned-yak-calves
#15
Quhani Peng, Nazir Ahmad Khan, B Xue, T H Yan, Z S Ahmad Wang
Objective: Yak is anone of the most important livestock species in the alpine-meadow grasslands of Qinghai-Tibetan plateau. WeThis study evaluated the effects of different levels of protein concentrate supplementation on the growth performance of yak calves, and correlated the growth rate to the changes occurring in the plasma- amino acids, and -insulin profile, and to the signaling activity of mammalian target of rapamycin (mTOR) cascade, in order to characterize the mechanism through which the protein synthesis can be improved in early weaned yaks...
June 27, 2017: Asian-Australasian Journal of Animal Sciences
https://www.readbyqxmd.com/read/28711648/alteration-of-pdgfr%C3%AE-akt-mtor-pathway-signaling-in-fibrosarcomatous-transformation-of-dermatofibrosarcoma-protuberans
#16
Yuka Hiraki-Hotokebuchi, Yuichi Yamada, Kenichi Kohashi, Hidetaka Yamamoto, Makoto Endo, Nokitaka Setsu, Kuma Yuki, Takamichi Ito, Yukihide Iwamoto, Masutaka Furue, Yoshinao Oda
Dermatofibrosarcoma protuberans (DFSP) is a cutaneous mesenchymal tumor of intermediate malignancy and fibroblastic/myofibroblastic differentiation. Fibrosarcomatous (FS) component is a high-grade component of DFSP. The detailed oncogenic difference between DFSP and FS components is not clear. We thus investigated the Akt-mTOR pathway in both components. We used 65 tumor samples obtained from 65 patients. The phosphorylation of Akt-mTOR pathway proteins (Akt, mTOR, 4EBP1, and S6RP) and PDGFRα/β was assessed by immunohistochemical staining, the results of which were confirmed by Western blotting...
September 2017: Human Pathology
https://www.readbyqxmd.com/read/28696243/inhibiting-4ebp1-in-glioblastoma
#17
Qi Wen Fan, Theodore P Nicolaides, William A Weiss
Glioblastoma is the most common and aggressive adult brain cancer. Tumors show frequent dysregulation of the phosphatidylinositol-3 kinase-mechanistic target of rapamycin pathway. While a number of small molecules target the PI3K-AKT-mTOR axis, their preclinical and clinical efficacy has been limited. Reasons for treatment failure include poor penetration of agents into the brain, and observations that blockade of PI3K or AKT minimally affects downstream mTOR activity in glioma. Clinical trials using allosteric mTOR inhibitors (rapamycin and rapalogs) to treat glioblastoma patients have also been unsuccessful or uncertain, in-part because rapamycin inefficiently blocks the mTORC1 target 4EBP1, and also feeds back to activate PI3K-AKT signaling...
July 10, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28664915/kinase-driven-metabolic-signalling-as-a-predictor-of-response-to-carboplatin-paclitaxel-adjuvant-treatment-in-advanced-ovarian-cancers
#18
Maria Isabella Sereni, Elisa Baldelli, Guido Gambara, Antonella Ravaggi, K Alex Hodge, David S Alberts, Jose M Guillen-Rodriguez, Ting Dong, Maurizio Memo, Franco Odicino, Roberto Angioli, Lance A Liotta, Sergio L Pecorelli, Emanuel F Petricoin, Mariaelena Pierobon
BACKGROUND: The biological mechanisms underlying early- and advanced-stage epithelial ovarian cancers (EOCs) are still poorly understood. This study explored kinase-driven metabolic signalling in early and advanced EOCs, and its role in tumour progression and response to carboplatin-paclitaxel treatment. METHODS: Tumour epithelia were isolated from two independent sets of primary EOC (n=72 and 30 for the discovery and the validation sets, respectively) via laser capture microdissection...
August 8, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28656204/effects-of-bufalin-on-the-mtor-p70s6k-pathway-and-apoptosis-in-esophageal-squamous-cell-carcinoma-in-nude-mice
#19
Yao Liu, Xu Wang, Ying Jia, Yueping Liu
The aim of this study was to investigate the effects of bufalin on the mammalian target of rapamycin (mTOR/p70S6 kinase (p70S6K) signaling pathway and cell apoptosis in orthotopically transplanted tumors in nude mice. The mice were inoculated with human esophageal squamous cell carcinoma (ESCC) ECA109 cells in order to establish a model of orthotopicall transplanted ESCC tumors. The mice are administered low, medium and high doses of bufalin (0.5, 1.0 and 1.5 mg/kg) or rapamycin, or a combination of both...
June 23, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28612529/-the-mechanism-of-combination-using-mtorc1-2-inhibitor-and-imatinib-to-suppress-cell-proliferation-of-ph-all-cell-line
#20
Jia-Hui Wu, Fang-Fang Shi, Yu-Ping Gong, Rui Shi
OBJECTIVES: To investigate the anti-leukemia effect and mechanism of mTORC1/2 inhibitor PP242 combined with imatinib (IM) on the proliferation of Ph(+) acute lymphoblastic leukemia (ALL) cell line SUP-B15. METHODS: SUP-B15 cell line was treated with PP242, imatinib (IM), or PP242 plus IM for 72 h, IC50 values (the concentration of drug required to kill 50% of the cells) and the combination index (CI ) of synergistic cytotoxicity was determined using MTT methods...
March 2017: Sichuan da Xue Xue Bao. Yi Xue Ban, Journal of Sichuan University. Medical Science Edition
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