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https://www.readbyqxmd.com/read/28822191/-polydatin-induces-human-cervical-cancer-cell-apoptosis-via-pi3k-akt-mtor-signaling-pathway
#1
Ji-Hong Pan, Hai-Bin Wang, Xiao-Fei Du, Jiang-Yue Liu, Dai-Juan Zhang
To observe the effect of polydatin on proliferation and apoptosis of cervical cancer HeLa cells and explore its possible mechanism. The growth inhibitory effect was detected with MTT assay. After HeLa cells were treated with different concentrations (50, 100, 150 μmol•L⁻¹) of polydatin, MTT assay was used to detect the inhibitory effect of polydatin on proliferation of HeLa cells; Acridine orange/ethidium bromide staining was used for morphological changes in apoptotic HeLa cells; Annexin/propidium iodide staining was applied to detect HeLa cell apoptotic rate...
June 2017: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://www.readbyqxmd.com/read/28821999/developmental-neurotoxicity-of-the-hippocampus-following-in-utero-exposure-to-methylmercury-impairment-in-cell-signaling
#2
Luana Heimfarth, Jeferson Delgado, Moara Rodrigues Mignori, Daniel Pens Gelain, José Cláudio Fonseca Moreira, Regina Pessoa-Pureur
In this study, we assessed some hippocampal signaling cascades and behavioral impairments in 30-day-old rat pups prenatally exposed to methylmercury (MeHg). Pregnant rats were exposed to 1.0 or 2.0 mg/kg MeHg by gavage in alternated days from gestational day 5 until parturition. We found increased anxiety-like and decreased exploration behavior evaluated by open field test and deficit of both short- and long-term memories by novel object recognition task, respectively, in MeHg-treated pups. Downregulated PI3K/Akt/mTOR pathway and activated/hypophosphorylated (Ser9) GSK3β in MeHg-treated pups could be upstream of hyperphosphorylated Tau (Ser396) destabilizing microtubules and contributing to neural dysfunction in the hippocampus of these rats...
August 18, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28817203/the-combination-of-digoxin-and-gsk2606414-exerts-synergistic-anticancer-activity-against-leukemia-in-vitro-and-in-vivo
#3
Xue-Hong Zhang, Xin-Yu Wang, Zhi-Wei Zhou, Hua Bai, Lin Shi, Yin-Xue Yang, Shu-Feng Zhou, Xiao-Chun Zhang
Digoxin is a member of cardiac glycosides and recent studies show that digoxin plays anticancer role in several types of cancer. However, the anticancer effects and mechanism of digoxin in leukemia is largely unknown. Her, our data show that digoxin treatment significantly inhibits leukemia cell viability. In addition, digoxin treatment significantly induced apoptosis and G2/M cell cycle arrest in leukemia cells. Furthermore, we demonstrated that digoxin treatment inactivate that oncogenic pathway Akt/mTOR signaling in leukemia cells...
August 17, 2017: BioFactors
https://www.readbyqxmd.com/read/28816646/chronic-cigarette-smoke-mediated-global-changes-in-lung-mucoepidermoid-cells-a-phosphoproteomic-analysis
#4
Hitendra S Solanki, Jayshree Advani, Aafaque Ahmad Khan, Aneesha Radhakrishnan, Nandini A Sahasrabuddhe, Sneha M Pinto, Xiaofei Chang, Thottethodi Subrahmanya Keshava Prasad, Premendu Prakash Mathur, David Sidransky, Harsha Gowda, Aditi Chatterjee
Proteomics analysis of chronic cigarette smoke exposure is a rapidly emerging postgenomics research field. While smoking is a major cause of lung cancer, functional studies using proteomics approaches could enrich our mechanistic understanding of the elusive lung cancer global molecular signaling and cigarette smoke relationship. We report in this study on a stable isotope labeling by amino acids in cell culture-based quantitative phosphoproteomic analysis of a human lung mucoepidermoid carcinoma cell line, H292 cells, chronically exposed to cigarette smoke...
August 2017: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/28815372/do-trpv1-antagonists-increase-the-risk-for-skin-tumourigenesis-a-collaborative-in-vitro-and-in-vivo-assessment
#5
Miyoung Park, Anita A Naidoo, Angie Burns, Jin Kyu Choi, Kelly M Gatfield, Martin Vidgeon-Hart, Il-Hong Bae, Chang Seok Lee, Gyeyoung Choi, Andrew J Powell, Young-Ho Park, Rajni Fagg
A recent hypothesis suggesting that the pharmacological target TRPV1 (transient receptor potential vanilloid subfamily, member 1) may function as a tumour suppressor, which potentially impacts the development of TRPV1 antagonist therapeutics for a range of conditions. However, little is known about the long-term physiologic effects of TRPV1 blockade in the skin. In vitro and in vivo studies suggested that the potent TRPV1 competitive antagonist AMG-9810 promoted proliferation in N/TERT1 cells (telomerase-immortalised primary human keratinocytes 1) and tumour development in mouse skin that was mediated through EGFR/Akt/mTOR signalling...
August 16, 2017: Cell Biology and Toxicology
https://www.readbyqxmd.com/read/28814333/rapamycin-prevents-cyclophosphamide-induced-over-activation-of-primordial-follicle-pool-through-pi3k-akt-mtor-signaling-pathway-in-vivo
#6
Linyan Zhou, Yanqiu Xie, Song Li, Yihua Liang, Qi Qiu, Haiyan Lin, Qingxue Zhang
BACKGROUND: Primordial follicular depletion has thought to be a common adverse effect of chemotherapy especially for female of reproductive age. The study aimed to evaluate the protective effect of rapamycin on the primordial follicles and its potential mechanism for patients receiving chemotherapy. METHODS: 8-week old BALB/c female mice were randomly assigned into four groups (control; rapamycin; cyclophosphamide; and rapamycin combined with cyclophosphamide). Hematoxylin staining, immunohistochemical, TUNEL, western blotting and ELISA were employed to assess inter-group differences using Student's t-test and Mann-Whitney test...
August 16, 2017: Journal of Ovarian Research
https://www.readbyqxmd.com/read/28811711/fibroblast-derived-cxcl12-sdf-1%C3%AE-promotes-cxcl6-secretion-and-co-operatively-enhances-metastatic-potential-through-the-pi3k-akt-mtor-pathway-in-colon-cancer
#7
Jia-Chi Ma, Xiao-Wen Sun, He Su, Quan Chen, Tian-Kang Guo, Yuan Li, Xiao-Chang Chen, Jin Guo, Zhen-Qiang Gong, Xiao-Dan Zhao, Jian-Bo Qi
AIM: To investigate the underlying mechanism by which CXCL12 and CXCL6 influences the metastatic potential of colon cancer and internal relation of colon cancer and stromal cells. METHODS: Western blotting was used to detect the expression of CXCL12 and CXCL6 in colon cancer cells and stromal cells. The co-operative effects of CXCL12 and CXCL6 on proliferation and invasion of colon cancer cells and human umbilical vein endothelial cells (HUVECs) were determined by enzyme-linked immunosorbent assay, and proliferation and invasion assays...
July 28, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28811636/mussel-inspired-polynorepinephrine-functionalized-electrospun-polycaprolactone-microfibers-for-muscle-regeneration
#8
Ying Liu, Guoqiang Zhou, Zhu Liu, Mengyu Guo, Xiumei Jiang, Mehmet Berat Taskin, Zhongyang Zhang, Jing Liu, Jinglong Tang, Ru Bai, Flemming Besenbacher, Menglin Chen, Chunying Chen
Electrospun scaffolds with excellent mechanical properties, high specific surface area and a commendable porous network are widely used in tissue engineering. Improving the hydrophilicity and cell adhesion of hydrophobic substrates is the key point to enhance the effectiveness of electrospun scaffolds. In this study, polycaprolactone (PCL) fibrous membranes with appropriate diameter were selected and coated by mussel-inspired poly norepinephrine (pNE). And norepinephrine is a catecholamine functioning as a hormone and neurotransmitter in the human brain...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28810331/-effect-of-tsc2-gene-expression-downregulation-by-lentivirus-induced-rna-interference-on-u937-cell-line-and-its-mechanism
#9
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/28808215/ginkgol-c17-1-inhibits-tumor-growth-by-blunting-the-egf-pi3k-akt-signaling-pathway
#10
Yueying Li, Jun Liu, Xiaoming Yang, Yan Dong, Yali Liu, Min Chen
Ginkgol C17:1 has been shown to inhibit apoptosis and migration of cancer cells, but the underlying mechanisms are not fully elucidated. In this study, we explored whether the inhibitory effects of Ginkgol C17:1 were associated with epidermal growth factor receptor (EGFR) and PI3K/Akt signaling. The results showed that EGF treatment increased the phosphorylation of EGFR, PI3K, Akt, mTOR and NF-kB, and also enhanced the proliferation, migration and invasion of HepG2 cells. Ginkgol C17:1 dose-dependently inhibited EGF-induced phosphorylation/activation of all the key components including EGFR, PI3K, Akt, mTOR and NF-kB, leading to a significant reduction either of proliferation or migration and invasion of HepG2 cells...
January 19, 2017: Journal of Biomedical Research
https://www.readbyqxmd.com/read/28807933/mice-deficient-in-lysophosphatidic-acid-acyltransferase-%C3%AE-lpaat%C3%AE-acylglycerophosphate-acyltransferase-4-agpat4-have-impairments-in-spatial-learning-and-memory-associated-with-reductions-in-nmda-and-ampa-receptors
#11
Ryan M Bradley, Emily B Mardian, Darin Bloemberg, Juan J Aristizabal Henao, Andrew S Mitchell, Phillip M Marvyn, Katherine A Moes, Ken D Stark, Joe Quadrilatero, Robin E Duncan
We previously characterized LPAATδ/AGPAT4 as a mitochondrial lysophosphatidic acid acyltransferase that regulates brain levels of phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylinositol (PI). Here we report that Lpaatδ (-/-) mice display impaired spatial learning and memory compared to wildtype littermates in the Morris Water Maze, and investigated potential mechanisms associated with brain phospholipid changes. Marker protein immunoblotting suggested that the relative brain content of neurons, glia, and oligodendrocytes was unchanged...
August 14, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28806782/the-use-of-18f-fluoro-deoxy-glucose-positron-emission-tomography-18f-fdg-pet-as-a-non-invasive-pharmacodynamic-biomarker-to-determine-the-minimally-pharmacologically-active-dose-of-azd8835-a-novel-pi3k%C3%AE-inhibitor
#12
Juliana Maynard, Sally-Ann Emmas, Francois-Xavier Ble, Herve Barjat, Emily Lawrie, Urs Hancox, Urszula M Polanska, Alison Pritchard, Kevin Hudson
BACKGROUND: The phosphatidyl inositol 3 kinase (PI3K), AKT and mammalian target of rapamycin (mTOR) signal transduction pathway is frequently de-regulated and activated in human cancer and is an important therapeutic target. AZD8835 is a PI3K inhibitor, with selectivity against PI3K α and δ isoforms, which is currently in Phase 1 clinical trials. 18F-Fluoro-deoxy-glucose positron emission tomography (18F-FDG PET) is a non-invasive pharmacodynamic imaging biomarker that has become an integral part of drug development...
2017: PloS One
https://www.readbyqxmd.com/read/28805979/effects-of-mtor-inhibition-on-cardiac-and-adipose-tissue-pathology-and-glucose-metabolism-in-rats-with-metabolic-syndrome
#13
Ayako Uchinaka, Mamoru Yoneda, Yuichiro Yamada, Toyoaki Murohara, Kohzo Nagata
The mammalian target of rapamycin (mTOR) is a regulator of metabolism and is implicated in pathological conditions such as obesity and diabetes. We aimed to investigate the role of mTOR in obesity. A new animal model of metabolic syndrome (MetS), named DahlS.Z-Lepr(fa) /Lepr(fa) (DS/obese) rats was established previously in our laboratory. In this study, we used this model to evaluate the effects of mTOR inhibition on cardiac and adipose tissue pathology and glucose metabolism. DS/obese rats were treated with the mTOR inhibitor, everolimus, (0...
August 2017: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28804535/hongjingtian-injection-attenuates-myocardial-oxidative-damage-via-promoting-autophagy-and-inhibiting-apoptosis
#14
Shujing Zhang, Ling Zhang, Han Zhang, Guanwei Fan, Jiuwen Qiu, Zongbao Fang, Haibo Wu, Yi Wang, Xiaoping Zhao
Natural products with antioxidative activities are widely applied to prevent and treat various oxidative stress related diseases, including ischemic heart disease. However, the cellular and molecular mechanisms of those therapies are still needed to be illustrated. In this study, we characterized the cardioprotective effects of Hongjingtian Injection (HJT), an extensively used botanical drug for treating coronary heart disease. The H/R-induced profound elevation of oxidative stress was suppressed by HJT. HJT also attenuates oxidative injury by promoting cell viability, intracellular ATP contents, and mitochondrial oxygen consumption...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28803490/parkin-pink1-and-dj1-as-possible-modulators-of-mtor-pathway-in-ganglioglioma
#15
Katarzyna Drapalo, Jaroslaw Jozwiak
Ganglioglioma (GG) is a non-malignant tumor classified as G1 by the WHO. Although we currently know that the neoplasm may result from the hyperactivity of protein kinase B (PKB or Akt) or extracellular-regulated kinase (Erk), which upregulates mammalian target of rapamycin kinase (mTOR) and leads to translation of proteins responsible for cell cycle regulation, there are still many questions to be answered. In the current paper we try to analyze the link between GG formation and activity of three proteins known to play a role in neuroprotection...
August 14, 2017: International Journal of Neuroscience
https://www.readbyqxmd.com/read/28803046/design-synthesis-and-biological-evaluation-of-novel-pyrazolochalcones-as-potential-modulators-of-pi3k-akt-mtor-pathway-and-inducers-of-apoptosis-in-breast-cancer-cells
#16
Anver Basha Shaik, Garikapati Koteswara Rao, G Bharath Kumar, Nibeditha Patel, Vangala Santhosh Reddy, Irfan Khan, Sunitha Rani Routhu, C Ganesh Kumar, Immadi Veena, Kunta Chandra Shekar, Madan Barkume, Shailesh Jadhav, Aarti Juvekar, Jyoti Kode, Manika Pal-Bhadra, Ahmed Kamal
Cancer has been established as the "Emperor of all maladies". In recent years, medicinal chemistry has focused on identifying novel anti-cancer compounds; though discovery of these compounds appears to be a herculean task. In present study, we synthesized forty pyrazolochalcone conjugates and explored their cytotoxic activity against a panel of sixty cancer cell lines. Fifteen conjugates of the series showed excellent growth inhibition (13b-e, 13h-j, 14c-d, 15 a, 15 c-d, 16b, 16d and 18f; GI50 for MCF-7: 0...
July 25, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28802917/aerobic-exercise-in-adolescence-results-in-an-increase-of-neuronal-and-non-neuronal-cells-and-in-mtor-overexpression-in-the-cerebral-cortex-of-rats
#17
Angélica Begatti Victorino, Fernando Tadeu Serra, Pâmella Pimentel Piñero, Alexandre Aparecido de Almeida, Glauber Menezes Lopim, Ivair Matias Junior, Helio Rubens Machado, Roberto Lent, Francisco Romero Cabral, Fernando Gomez-Pinilla, Ricardo Mario Arida, Sérgio Gomes da Silva
Better cognitive performance and greater cortical and hippocampal volume have been observed in individuals who undertook aerobic exercise during childhood and adolescence. One possible explanation for these beneficial effects is that juvenile physical exercise enables better neural development and hence more cells and neuronal circuitries. It is probable that such effects occur through intracellular signaling proteins associated with cell growth, proliferation and survival. Based on this information, we evaluated the number of neuronal and non-neuronal cells using isotropic fractionation and the expression and activation of intracellular proteins (ERK, CREB Akt, mTOR and p70S6K) in the cerebral cortex and hippocampal formation of the rats submitted to a physical exercise program on a treadmill during adolescence...
August 9, 2017: Neuroscience
https://www.readbyqxmd.com/read/28802652/an-autophagic-mechanism-is-involved-in-the-6-hydroxydopamine-induced-neurotoxicity-in-vivo
#18
Xin He, Wei Yuan, Zijian Li, Juan Feng
6-hydroxydopamine (6-OHDA) is one of the most common agents for modeling dopaminergic neuron degeneration in Parkinson's disease (PD). So far, the role of autophagy in 6-OHDA-induced neurotoxicity remains controversial and most evidence is collected from in vitro studies. In this study, we determined the role of autophagy activation in 6-OHDA-induced neurotoxicity in a rat model of PD. Following 6-OHDA treatment, we observed a concomitant activation of autophagy and apoptosis. To further explore the interaction between autophagy and apoptosis induced by 6-OHDA, autophagy inhibitor 3-methylademine (3-MA) or cysteine protease inhibitor Z-FA-fmk was applied...
August 9, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28802252/exploiting-radiation-induced-signaling-to-increase-the-susceptibility-of-resistant-cancer-cells-to-targeted-drugs-akt-and-mtor-inhibitors-as-an-example
#19
Iris Eke, Adeola Y Makinde, Molykutty J Aryankalayil, Veit Sandfort, Sanjeewani T Palayoor, Barbara H Rath, Lance Liotta, Mariaelena Pierobon, Emanuel F Petricoin, Matthew F Brown, Jayne M Stommel, Mansoor M Ahmed, C Norman Coleman
Implementing targeted drug therapy in radio-oncologic treatment regimens has greatly improved the outcome of cancer patients. However, the efficacy of molecular targeted drugs such as inhibitory antibodies or small molecule inhibitors essentially depends on target expression and activity, which both can change during the course of treatment. Radiotherapy has previously been shown to activate pro-survival pathways which can help tumor cells to adapt and thereby survive treatment. Therefore, we aimed to identify changes in signaling induced by radiation and evaluate the potential of targeting these changes with small molecules to increase the therapeutic efficacy on cancer cell survival...
August 11, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28801921/autophagy-impairment-by-caspase-1-dependent-inflammation-mediates-memory-loss-in-response-to-%C3%AE-amyloid-peptide-accumulation
#20
Lourdes Álvarez-Arellano, Martha Pedraza-Escalona, Tonali Blanco-Ayala, Nohemí Camacho-Concha, Javier Cortés-Mendoza, Leonor Pérez-Martínez, Gustavo Pedraza-Alva
β-Amyloid peptide accumulation in the cortex and in the hippocampus results in neurodegeneration and memory loss. Recently, it became evident that the inflammatory response triggered by β-Amyloid peptides promotes neuronal cell death and degeneration. In addition to inflammation, β-Amyloid peptides also induce alterations in neuronal autophagy, eventually leading to neuronal cell death. Thus, here we evaluated whether the inflammatory response induced by the β-Amyloid peptides impairs memory via disrupting the autophagic flux...
August 12, 2017: Journal of Neuroscience Research
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