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https://www.readbyqxmd.com/read/28526373/coffee-consumption-in-aged-mice-increases-energy-production-and-decreases-hepatic-mtor-levels
#1
Keita Takahashi, Shuichi Yanai, Kentaro Shimokado, Akihito Ishigami
OBJECTIVE: Coffee, one of the world's most consumed beverages, has many benefits. Some studies have reported the effects of coffee on aging. The aim of this study was to investigate the locomotor activity, energy metabolism, and lipid metabolism of aged (20-mo-old) mice given coffee. METHODS: Aged C57 BL/6 NCr mice were divided into three groups: controls that were not given coffee (n = 9), a group that received 0.1% caffeinated coffee (n = 9), and a group that received 0...
June 2017: Nutrition
https://www.readbyqxmd.com/read/28522824/obestatin-controls-skeletal-muscle-fiber-type-determination
#2
Icía Santos-Zas, Tania Cid-Díaz, Jessica González-Sánchez, Uxía Gurriarán-Rodriguez, Carlos Seoane-Mosteiro, Begoña Porteiro, Rubén Nogueiras, Xesús Casabiell, José Luis Relova, Rosalía Gallego, Vincent Mouly, Yolanda Pazos, Jesus P Camiña
Obestatin/GPR39 signaling stimulates skeletal muscle growth and repair by inducing both G-protein-dependent and -independent mechanisms linking the activated GPR39 receptor with distinct sets of accessory and effector proteins. In this work, we describe a new level of activity where obestatin signaling plays a role in the formation, contractile properties and metabolic profile of skeletal muscle through determination of oxidative fiber type. Our data indicate that obestatin regulates Mef2 activity and PGC-1α expression...
May 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28515304/ros-mediated-jnk-activation-contributes-to-hbx-induced-autophagy-via-regulating-beclin-1-bcl-2-interaction
#3
Linmao Zhong, Wanqin Shu, Wangbin Dai, Bo Gao, Sidong Xiong
Autophagy is closely associated with the regulation of Hepatitis B virus (HBV) replication. HBV X protein (HBx), a multifunctional regulator in HBV-associated biological processes, has been demonstrated to be crucial for the autophagy induction by HBV. However, the molecular mechanisms of autophagy induction by HBx, especially the signaling pathways involved, remain still elusive. In present investigation, we demonstrated that HBx induced autophagosome formation independent of class I phosphatidylinositol-3 kinase (PI3K)/AKT/mTOR signaling pathway...
May 17, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28508346/testosterone-insulin-like-effects-an-in-vitro-study-on-the-short-term-metabolic-effects-of-testosterone-in-human-skeletal-muscle-cells
#4
C Antinozzi, F Marampon, C Corinaldesi, E Vicini, P Sgrò, G B Vannelli, A Lenzi, C Crescioli, L Di Luigi
PURPOSE: Testosterone by promoting different metabolic pathways contributes to short-term homeostasis of skeletal muscle, the largest insulin-sensitive tissue and the primary site for insulin-stimulated glucose utilization. Despite evidences indicate a close relationship between testosterone and glucose metabolism, the molecular mechanisms responsible for a possible testosterone-mediated insulin-like effects on skeletal muscle are still unknown. METHODS: Here we used undifferentiated proliferating or differentiated human fetal skeletal muscle cells (Hfsmc) to investigate the short-term effects of testosterone on the insulin-mediated biomolecular metabolic machinery...
May 15, 2017: Journal of Endocrinological Investigation
https://www.readbyqxmd.com/read/28484273/role-of-akt-independent-mtorc1-and-gsk3%C3%AE-signaling-in-sublethal-nmda-induced-injury-and-the-recovery-of-neuronal-electrophysiology-and-survival
#5
Przemyslaw Swiatkowski, Ina Nikolaeva, Gaurav Kumar, Avery Zucco, Barbara F Akum, Mihir V Patel, Gabriella D'Arcangelo, Bonnie L Firestein
Glutamate-induced excitotoxicity, mediated by overstimulation of N-methyl-D-aspartate (NMDA) receptors, is a mechanism that causes secondary damage to neurons. The early phase of injury causes loss of dendritic spines and changes to synaptic activity. The phosphatidylinositol-4,5-bisphosphate 3-kinase/Akt/ mammalian target of rapamycin (PI3K/Akt/mTOR) pathway has been implicated in the modulation and regulation of synaptic strength, activity, maturation, and axonal regeneration. The present study focuses on the physiology and survival of neurons following manipulation of Akt and several downstream targets, such as GSK3β, FOXO1, and mTORC1, prior to NMDA-induced injury...
May 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28479388/acceleration-based-training-a-new-mode-of-training-in-senescent-rats-improving-performance-and-left-ventricular-and-muscle-functions
#6
Thierry Launay, Iman Momken, Serge Carreira, Nathalie Mougenot, Xian-Long Zhou, Leanne De Koning, Romain Niel, Bruno Riou, Véronique Billat, Sophie Besse
High intensity training (HIT) has been shown to improve maximal aerobic capacity and muscle protein synthesis but has not yet been investigated in senescent rats. We hypothesized that the change of speed (acceleration) during each bout of HIT acts as a stimulus responsible for the adaptations of the organism to exercise. Twenty two month-old (mo) rats (n=14) were subjected to a short acceleration protocol (20-30min) of exercise, comprising 3 independent bouts of acceleration and compared to an age-matched sedentary group (n=14)...
May 4, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28446728/inhibition-of-hsf1-suppresses-the-growth-of-hepatocarcinoma-cell-lines-in-vitro-and-akt-driven-hepatocarcinogenesis-in-mice
#7
Antonio Cigliano, Chunmei Wang, Maria G Pilo, Marta Szydlowska, Stefania Brozzetti, Gavinella Latte, Giovanni M Pes, Rosa M Pascale, Maria A Seddaiu, Gianpaolo Vidili, Silvia Ribback, Frank Dombrowski, Matthias Evert, Xin Chen, Diego F Calvisi
Upregulation of the heat shock transcription factor 1 (HSF1) has been described as a frequent event in many cancer types, but its oncogenic role in hepatocellular carcinoma (HCC) remains poorly delineated. In the present study, we assessed the function(s) of HSF1 in hepatocarcinogenesis via in vitro and in vivo approaches. In particular, we determined the importance of HSF1 on v-Akt murine thymoma viral oncogene homolog (AKT)-induced liver cancer development in mice. We found that knockdown of HSF1 activity via specific siRNA triggered growth restraint by suppressing cell proliferation and inducing massive cell apoptosis in human HCC cell lines...
April 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28446508/enrichment-of-pik3-akt-mtor-pathway-activation-in-hepatic-metastases-from-breast-cancer
#8
Mariaelena Pierobon, Corrine Ramos, Shukmei Wong, K Alex Hodge, Jessica Aldrich, Sara A Byron, Stephen P Anthony, Nicholas J Robert, Donald W Northfelt, Mohammad Jahanzeb, Linda Vocila, Julia D Wulfkuhle, Guido Gambara, Rosa Isela Gallagher, Bryant Dunetz, Nicholas Hoke, Ting Dong, David W Craig, Massimo Cristofanilli, Brian Leyland Jones, Lance Liotta, Joyce A O'Shaughnessy, John D Carpten, Emanuel F Petricoin
Purpose: Little is known about the molecular signatures associated with specific metastatic sites in breast cancer. Using comprehensive multi-omic molecular profiling, we assessed whether alterations or activation of the PI3K-AKT-mTOR pathway is associated with specific sites of breast cancer metastasis. <p>Experimental Design: NGS-based whole exome sequencing was coupled with Reverse Phase Protein Microarray (RPPA) functional signaling network analysis to explore the PI3K-AKT-mTOR axis in 32 pretreated breast cancer metastases...
April 26, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28442505/overexpressed-fatty-acid-synthase-in-gastrointestinal-stromal-tumors-targeting-a-progression-associated-metabolic-driver-enhances-the-antitumor-effect-of-imatinib
#9
Chien-Feng Li, Fu-Min Fang, Yeng-Yang Chen, Ting-Ting Liu, Ti-Chun Chan, Shih-Chen Yu, Li-Tzong Chen, Hsuan-Ying Huang
Purpose: In gastrointestinal stromal tumors (GISTs), lipid-metabolizing enzymes remain underexplored, including fatty acid synthase (FASN). <p>Experimental Design: Forty GISTs were quantitated for FASN mRNA abundance. FASN immunoexpression was informative in 350 GISTs, including 213 with known KIT/PDGFRA/BRAF genotypes. In imatinib-resistant FASN-overexpressing GIST cells, the roles of overexpressed FASN and FASN-targeting C75 in tumor phenotypes, apoptosis and autophagy, KIT transcription, PI3K/AKT/mTOR activation, and imatinib resistance were analyzed by RNA interference or myristoylated-AKT transfection...
April 25, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28422956/chronic-activation-of-ppar%C3%AE-with-fenofibrate-reduces-autophagic-proteins-in-the-liver-of-mice-independent-of-fgf21
#10
Eunjung Jo, Songpei Li, Qingning Liang, Xinmei Zhang, Hao Wang, Terence P Herbert, Trisha A Jenkins, Aimin Xu, Ji-Ming Ye
Autophagy is a catabolic mechanism to degrade cellular components to maintain cellular energy levels during starvation, a condition where PPARα may be activated. Here we report a reduced autophagic capacity in the liver following chronic activation of PPARα with fenofibrate (FB) in mice. Chronic administration of the PPARα agonist FB substantially reduced the levels of multiple autophagy proteins in the liver (Atg3, Agt4B, Atg5, Atg7 and beclin 1) which were associated with a decrease in the light chain LC3II/LC3I ratio and the accumulation of p62...
2017: PloS One
https://www.readbyqxmd.com/read/28410220/reprogramming-induced-by-isoliquiritigenin-diminishes-melanoma-cachexia-through-mtorc2-akt-gsk3%C3%AE-signaling
#11
Xiao-Yu Chen, De-Fang Li, Ji-Chun Han, Bo Wang, Zheng-Ping Dong, Li-Na Yu, Zhao-Hai Pan, Chuan-Jun Qu, Ying Chen, Shi-Guo Sun, Qiu-Sheng Zheng
Isoliquiritigenin (ISL), a member of the flavonoids, is known to have anti-tumor activity in vitro and in vivo. The effect of ISL on reprogramming in cancer cells, however, remains elusive. In this study, we investigated the effect of ISL on reprogramming in human melanoma A375 cells. ISL (15 μg/ml) significantly inhibited A375 cell proliferation, anchorage independent cell proliferation and G2/M cell cycle arrest after ISL exposure for 24 h. However, there were no significant changes in apoptosis rate. Terminal differentiation indicators (melanin content, melanogenesis mRNA expression, tyrosinase (TYR) activity) were all up-regulated by ISL treatment...
March 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28396841/ubiquitin-ligase-smurf1-functions-as-a-prognostic-marker-and-promotes-growth-and-metastasis-of-clear-cell-renal-cell-carcinoma
#12
Mang Ke, Licai Mo, Weilin Li, Xianjun Zhang, Feiping Li, Hongyuan Yu
Smad ubiquitin regulatory factor 1 (SMURF1), a recently identified E3 ubiquitin ligase, targets substrate proteins for ubiquitination and proteasomal degradation. Previous studies have reported that SMURF1 also functions as an oncogene in human cancers. However, the clinical value of SMURF1 and its role in clear cell renal cell carcinoma (ccRCC) are unknown. SMURF1 expression was analyzed in 100 cases of ccRCC and matched tumor-adjacent specimens. SMURF1 was prominently overexpressed in ccRCC specimens compared with tumor-adjacent specimens...
April 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28396363/genomic-and-molecular-screenings-identify-different-mechanisms-for-acquired-resistance-to-met-inhibitors-in-lung-cancer-cells
#13
Pol Gimenez-Xavier, Eva Pros, Ester Bonastre, Sebastian Moran, Ana Aza, Osvaldo Graña, Gonzalo Gómez-López, Sophia Derdak, Marc Dabad, Anna Esteve-Codina, Jose R Hernandez Mora, Diana Salinas-Chaparro, Manel Esteller, David Pisano, Montse Sanchez-Cespedes
The development of resistance to tyrosine kinase inhibitors (TKIs) limits the long-term efficacy of cancer treatments involving them. We aimed to understand the mechanisms that underlie acquired resistance (AR) to MET inhibitors in lung cancer. EBC1 cells, which have MET amplification and are sensitive to TKIs against MET, were used to generate multiple clones with AR to a MET-TKI. Whole-exome sequencing, RNA sequencing and global DNA methylation analysis were used to scrutinize the genetic and molecular characteristics of the resistant cells...
April 10, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28392705/long-noncoding-rna-linc01296-is-associated-with-poor-prognosis-in-prostate-cancer-and-promotes-cancer-cell-proliferation-and-metastasis
#14
Jie Wu, Gong Cheng, Cheng Zhang, Yuxiao Zheng, Haoxiang Xu, Haiwei Yang, Lixin Hua
BACKGROUND/PURPOSE: Long noncoding RNAs (lncRNAs) have emerged as important regulators and biomarkers of tumor development and progression. This study investigated the clinical significance, biological functions, and underlying mechanisms of long intergenic non-protein-coding RNA 1296 (LINC01296) in prostate cancer. MATERIALS AND METHODS: LINC01296 expression in prostate cancer tissues and cell lines was detected by quantitative real-time polymerase chain reaction (qRT-PCR)...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28387249/lanatoside-c-a-cardiac-glycoside-acts-through-protein-kinase-c%C3%AE-to-cause-apoptosis-of-human-hepatocellular-carcinoma-cells
#15
Min-Wu Chao, Tzu-Hsuan Chen, Han-Li Huang, Yu-Wei Chang, Wei-Chun HuangFu, Yu-Ching Lee, Che-Ming Teng, Shiow-Lin Pan
Recent studies have revealed that cardiac glycosides, such as digitalis and digoxin, have anticancer activity and may serve as lead compounds for the development of cancer treatments. The poor prognosis of hepatocellular carcinoma (HCC) patients reflects the development of resistance to current chemotherapeutic agents, highlighting the need for discovering new small-molecule therapeutics. Here, we found that lanatoside C, an anti-arrhythmic agent extracted from Digitalis lanata, inhibited the growth of HCC cells and dramatically decreased tumor volume as well as delayed tumor growth without obvious body weight loss...
April 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28382169/integration-of-receptor-tyrosine-kinases-determines-sensitivity-to-pi3k%C3%AE-selective-inhibitors-in-breast-cancer
#16
Yi-Chao Xu, Xiang Wang, Yi Chen, Si-Meng Chen, Xin-Ying Yang, Yi-Ming Sun, Mei-Yu Geng, Jian Ding, Ling-Hua Meng
PI3Kα-selective inhibitor BYL719 is currently in phase II/III clinical trial for the treatment of breast cancer, but highly variable response has been observed among patients. We sought to discover predictive biomarker for the efficacy of BYL719 by dissecting the proliferative signaling pathway mediated by PI3K in breast cancer. BYL719 concurrently inhibited the phosphorylation of AKT and ERK in PIK3CA-mutated human breast cancer cells. PI3K-regulated ERK phosphorylation was independent of canonical PDK1/AKT/mTOR pathway, while it was associated with RAF/MEK...
2017: Theranostics
https://www.readbyqxmd.com/read/28380429/ccl5-establishes-an-autocrine-high-grade-glioma-growth-regulatory-circuit-critical-for-mesenchymal-glioblastoma-survival
#17
Yuan Pan, Laura J Smithson, Yu Ma, Dolores Hambardzumyan, David H Gutmann
Glioblastoma (GBM) is the most common malignant brain tumor in adults, with a median survival of 15 months. These poor clinical outcomes have prompted the development of drugs that block neoplastic cancer cell growth; however, non-neoplastic cell-derived signals (chemokines and cytokines) in the tumor microenvironment may also represent viable treatment targets. One such chemokine, Ccl5, produced by low-grade tumor-associated microglia, is responsible for maintaining neurofibromatosis type 1 (NF1) mouse optic glioma growth in vivo...
May 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28288862/autophagy-inhibits-c2-ceramide-mediated-cell-death-by-decreasing-the-reactive-oxygen-species-levels-in-sh-sy5y-cells
#18
Chenghe Fan, Yuanyuan Liu, Mingming Zhao, Rui Zhan, Wei Cui, Haiqiang Jin, Yuming Teng, Pu Lv, Lemin Zheng, Yining Huang
Ceramide has been recognized as a second messenger that regulates several intracellular processes in neuronal cells. However, its role in neuronal autophagy is not fully understood. In this study, we used a human neuroblastoma cell line (SH-SY5Y) to investigate the mechanisms underlying C2-ceramide-mediated cell death and autophagy. C2-ceramide induced caspase-3-independent cell death. In addition, C2-ceramide induced autophagy, decreased the activation of Akt and mTOR, and increased the activation of JNK and ERK1/2...
March 10, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28274614/metformin-represses-glucose-starvation-induced-autophagic-response-in-microvascular-endothelial-cells-and-promotes-cell-death
#19
Samson Mathews Samuel, Suparna Ghosh, Yasser Majeed, Gnanapragasam Arunachalam, Mohamed M Emara, Hong Ding, Chris R Triggle
Metformin, the most frequently administered drug for the treatment of type 2 diabetes, is being investigated for its potential in the treatment of various types of cancer; however, the cellular basis for this putative anti-cancer action remains controversial. In the current study we examined the effect of metformin on endoplasmic reticulum (ER) stress and autophagy in glucose-starved micro-vascular endothelial cells (MECs). The rationale for our experimental protocol is that in a growing tumor MECs are subjected to hypoxia and nutrient/glucose starvation that results from the reduced supply and relatively high consumption of glucose...
May 15, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28272775/cryptotanshinone-inhibition-of-mammalian-target-of-rapamycin-pathway-is-dependent-on-oestrogen-receptor-alpha-in-breast-cancer
#20
Yanhong Pan, Junfeng Shi, Wenting Ni, Yuping Liu, Siliang Wang, Xu Wang, Zhonghong Wei, Aiyun Wang, Wenxing Chen, Yin Lu
Cryptotanshinone (CPT) has been demonstrated to inhibit proliferation and mammalian target of rapamycin (mTOR) pathway in MCF-7 breast cancer cells. However, the same results are unable to be repeated in MDA-MB-231 cells. Given the main difference of oestrogen receptor α (ERα) between two types of breast cancer cells, It is possibly suggested that CPT inhibits mTOR pathway dependent on ERα in breast cancer. CPT could significantly inhibit cell proliferation of ERα-positive cancer cells, whereas ERα-negative cancer cells are insensitive to CPT...
March 8, 2017: Journal of Cellular and Molecular Medicine
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