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Y-X Cao, Z-Q Wang, J-X Kang, K Liu, C-F Zhao, Y-X Guo, B-H Jiao
OBJECTIVE: It's of great significance to investigate the novel targets of drugs for the treatment of stroke. In this study, we explored the neuroprotective role of miR-424 in oxygen glucose deprivation (OGD)-induced injuries in PC-12 cells. MATERIALS AND METHODS: PC-12 cells were subjected to OGD stimulation to mimic ischemic injury. The expressions of miR-424 and mitogen-activated protein kinase phosphatase-1 (MKP-1) were altered by transient transfection with miR-424 mimic, miR-424 inhibitor, pEX-MKP-1, or sh-MKP-1...
March 2018: European Review for Medical and Pharmacological Sciences
Liyuan Mao, Qiongyun Chen, Ke Gong, Xiaolin Xu, Yurou Xie, Wenqing Zhang, Hanwei Cao, Tianhui Hu, Xiaoting Hong, Yan-Yan Zhan
Hyperactivated glucose uptake and glycolytic metabolism are considered as a hallmark of cancer. Berberine, a natural alkaloid with tumor‑selective anticancer effects, has been shown to promote glucose uptake in metabolic tissues and cells. However, whether and how berberine regulates the glucose metabolism of cancer cells are still poorly understood. In the present study, we revealed that berberine, which suppressed the growth of colon cancer cell lines HCT116 and KM12C, greatly inhibited the glucose uptake and the transcription of glucose metabolic genes, GLUT1, LDHA and HK2 in these two cell lines as assessed by RT‑qPCR...
May 2018: Oncology Reports
Wenwen Wang, Juan Liu, Jianni Qi, Junyong Zhang, Qiang Zhu, Chengyong Qin
Following the publication of this article, we realize that the title appeared incorrectly: This appeared in print as 'RLIP76 increases apoptosis through Akt/mTOR signaling pathway in gastric cancer', and the corrected title is now featured above ('increases' should have read as 'decreases'). Note that this error did not have any bearing on the results reported in the paper (which were reported accurately in terms of the influence of RLIP76 on apoptosis of human gastric cancer SGC‑7901 and MGC‑803 cells), or the conclusions therein...
May 2018: Oncology Reports
Hsien-Kuo Chin, Chi-Ting Horng, Yi-Shan Liu, Chi-Cheng Lu, Chen-Ying Su, Pei-Syuan Chen, Hong-Yi Chiu, Fuu-Jen Tsai, Po-Chuen Shieh, Jai-Sing Yang
Anti-angiogenesis is one of the most general clinical obstacles in cancer chemotherapy. Kaempferol is a flavonoid phytochemical found in many fruits and vegetables. Our previous study revealed that kaempferol triggered apoptosis in human umbilical vein endothelial cells (HUVECs) by ROS‑mediated p53/ATM/death receptor signaling. However, the anti‑angiogenic potential of kaempferol remains unclear and its underlying mechanism warranted further exploration in VEGF‑stimulated HUVECs. In the present study, kaempferol significantly reduced VEGF‑stimulated HUVEC viability...
May 2018: Oncology Reports
Pau B Esparza-Moltó, José M Cuezva
Cancer cells reprogram energy metabolism by boosting aerobic glycolysis as a main pathway for the provision of metabolic energy and of precursors for anabolic purposes. Accordingly, the relative expression of the catalytic subunit of the mitochondrial H+ -ATP synthase-the core hub of oxidative phosphorylation-is downregulated in human carcinomas when compared with its expression in normal tissues. Moreover, some prevalent carcinomas also upregulate the ATPase inhibitory factor 1 (IF1), which is the physiological inhibitor of the H+ -ATP synthase...
2018: Frontiers in Oncology
Jason J Gokey, Anusha Sridharan, Yan Xu, Jenna Green, Gianni Carraro, Barry R Stripp, Anne-Karina T Perl, Jeffrey A Whitsett
Hippo/YAP signaling plays pleiotropic roles in the regulation of cell proliferation and differentiation during organogenesis and tissue repair. Herein we demonstrate increased YAP activity in respiratory epithelial cells in lungs of patients with idiopathic pulmonary fibrosis (IPF), a common, lethal form of interstitial lung disease (ILD). Immunofluorescence staining in IPF epithelial cells demonstrated increased nuclear YAP and loss of MST1/2. Bioinformatic analyses of epithelial cell RNA profiles predicted increased activity of YAP and increased canonical mTOR/PI3K/AKT signaling in IPF...
March 22, 2018: JCI Insight
Elke Tatjana Aristizabal Prada, Vera Heinzle, Thomas Knösel, Svenja Nölting, Gerald Spoettl, Julian Maurer, Christine Spitzweg, Martin Angele, Nina Schmidt, Felix Beuschlein, Günter K Stalla, Rainer Blaser, Klaus A Kuhn, Christoph J Auernhammer
Tropomyosin receptor kinase (Trk) inhibitors are investigated as a novel targeted therapy in various cancers. We investigated the in vitro effects of the pan-Trk inhibitor GNF-5837 in human neuroendocrine tumor (NET) cells. The human neuroendocrine pancreatic BON1, bronchopulmonary NCI-H727 and ileal GOT1 cell lines were treated with GNF-5837 alone and in combination with everolimus. Cell viability decreased in a time- and dose-dependent manner in GOT1 cells in response to GNF-5837 treatment, while treatment in BON1 and NCI-H727 cells showed no effect on cellular viability...
March 21, 2018: Endocrine-related Cancer
Zhouyang Li, Yinfang Wu, Haipin Chen, Chen Zhu, Lingling Dong, Yong Wang, Huiwen Liu, Xuchen Xu, Jiesen Zhou, Yanping Wu, Wen Li, Songmin Ying, Huahao Shen, Zhihua Chen
Increasing toxicological and epidemiological studies have demonstrated that ambient particulate matter (PM) could cause adverse health effects including inflammation in the lung. Alveolar macrophages represent a major type of innate immune responses to foreign substances. However, the detailed mechanisms of inflammatory responses induced by PM exposure in macrophages are still unclear. We observed that coarse PM treatment rapidly activated mechanistic target of rapamycin (MTOR) in mouse alveolar macrophages in vivo, and in cultured mouse bone marrow-derived macrophages, mouse peritoneal macrophages, and RAW264...
March 21, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Claudia Manzoni, Adamantios Mamais, Sybille Dihanich, Marc P M Soutar, Helene Plun-Favreau, Rina Bandopadhyay, Rosella Abeti, Paola Giunti, John Hardy, Mark Cookson, Sharon A Tooze, Patrick A Lewis
Unc-51 Like Kinase 1 (ULK1) is a critical regulator of the biogenesis of autophagosomes, the central component of the catabolic macroautophagy pathway. Regulation of ULK1 activity is dependent upon several phosphorylation events acting to repress or activate the enzymatic function of this protein. Phosphorylation of Ser758 ULK1 has been linked to repression of autophagosome biogenesis and was thought to be exclusively dependent upon mTOR complex 1 kinase activity. In this study, a novel regulation of Ser758 ULK1 phosphorylation is reported following prolonged inhibition of the Parkinson's disease linked protein Leucine Rich Repeat Kinase 2 (LRRK2)...
March 21, 2018: Bioscience Reports
Zhe Yang, Jordan Follett, Markus C Kerr, Thomas Clairfeuille, Mintu Chandra, Brett M Collins, Rohan D Teasdale
The Alanine, Serine, Cysteine-preferring Transporter 2 (ASCT2; SLC1A5) is responsible for the uptake of glutamine into cells, a major source of cellular energy and a key regulator of mammalian Target of Rapamycin (mTOR) activation. Furthermore, ASCT2 expression has reported in several human cancers making it a potential target for both diagnostic and therapeutic purposes. Here we identify ASCT2 as a membrane trafficked cargo molecule, sorted through a direct interaction with the PDZ domain of Sorting Nexin 27 (SNX27)...
March 21, 2018: Journal of Biological Chemistry
D Allan Butterfield, Debra Boyd-Kimball
Oxidative stress is implicated in the pathogenesis and progression of Alzheimer's disease (AD) and its earlier stage, amnestic mild cognitive impairment (aMCI). One source of oxidative stress in AD and aMCI brains is that associated with amyloid-β peptide, Aβ1-42 oligomers. Our laboratory first showed in AD elevated oxidative stress occurred in brain regions rich in Aβ1-42, but not in Aβ1-42-poor regions, and was among the first to demonstrate Aβ peptides led to lipid peroxidation (indexed by HNE) in AD and aMCI brains...
2018: Journal of Alzheimer's Disease: JAD
Wei Zhang, Guihai Feng, Libin Wang, Fei Teng, Liu Wang, Wei Li, Ying Zhang, Qi Zhou
The generation of induced pluripotent stem cells (iPSCs) offers a great opportunity in research and regenerative medicine. The current poor efficiency and incomplete mechanistic understanding of the reprogramming process hampers the clinical application of iPSCs. MeCP2 connects histone modification and DNA methylation, which are key changes of somatic cell reprogramming. However, the role of MeCP2 in cell reprogramming has not been examined. In this study, we found that MeCP2 deficiency enhanced reprogramming efficiency and stimulated cell proliferation through regulating cell cycle protein expression in the early stage of reprogramming...
March 19, 2018: Journal of Molecular Cell Biology
Sravanth K Hindupur, Marco Colombi, Stephen R Fuhs, Matthias S Matter, Yakir Guri, Kevin Adam, Marion Cornu, Salvatore Piscuoglio, Charlotte K Y Ng, Charles Betz, Dritan Liko, Luca Quagliata, Suzette Moes, Paul Jenoe, Luigi M Terracciano, Markus H Heim, Tony Hunter, Michael N Hall
Histidine phosphorylation, the so-called hidden phosphoproteome, is a poorly characterized post-translational modification of proteins. Here we describe a role of histidine phosphorylation in tumorigenesis. Proteomic analysis of 12 tumours from an mTOR-driven hepatocellular carcinoma mouse model revealed that NME1 and NME2, the only known mammalian histidine kinases, were upregulated. Conversely, expression of the putative histidine phosphatase LHPP was downregulated specifically in the tumours. We demonstrate that LHPP is indeed a protein histidine phosphatase...
March 21, 2018: Nature
Ting-Ting Liu, Xi-Sheng Liu, Meng Zhang, Xue-Ni Liu, Fu-Xiang Zhu, Fang-Ming Zhu, Si-Wen Ouyang, Shan-Bao Li, Chen-Long Song, Hui-Min Sun, Su Lu, Yu Zhang, Jun Lin, Hua-Mei Tang, Zhi-Hai Peng
PURPOSE: Recent studies have determined that cartilage oligomeric matrix protein (COMP) plays a vital role in carcinogenesis. We sought to clarify the role of COMP in colon cancer. METHODS: We investigated gene expression data from The Cancer Genome Atlas (TCGA) dataset. Tissue microarrays (TMA) containing paired samples from 253 patients with colon cancer were subjected to immunostaining. COMP levels in serum of colon cancer patients and healthy donors were measured with ELISA...
March 20, 2018: Journal of Cancer Research and Clinical Oncology
Xian-Qin Luo, Ao Li, Xue Yang, Xiao Xiao, Rong Hu, Tian-Wen Wang, Xiao-Yun Dou, Da-Jian Yang, Zhi Dong
Background: Cerebral hypoperfusion is a pivotal risk factor for vascular dementia (VD), for which effective therapy remains inadequate. Persistent inflammatory responses and excessive chemotaxis of microglia/macrophages in the brain may accelerate the progression of VD. Endocannabinoids are involved in neuronal protection against inflammation-induced neuronal injury. Cannabinoids acting at cannabinoid receptor 2 (CB2 R) can decrease inflammation. Based on the identification of paeoniflorin (PF) as a CB2 R agonist, we investigated the neuroprotective and microglia/macrophages M1 to M2 polarization promoting effects of PF in a permanent four-vessel occlusion rat model...
2018: Chinese Medicine
Zhiguo Li, Yifan Kong, Longzhen Song, Qian Luo, Jinghui Liu, Chen Shao, Xianzeng Hou, Xiaoqi Liu
The AKT/TSC/mTOR axis is an important pathway controlling cell growth, survival and proliferation in response to extracellular cues. Recently, it was reported that AKT activity fluctuates across the cell cycle. However, it remains unclear whether downstream targets of AKT are also regulated by the cell cycle. Here we report that mTORC1 activity inversely correlates with AKT activity during the cell cycle. Mechanistically, Plk1 phosphorylation of TSC1 at S467 and S578 interfered with TSC1/TSC2 binding, destabilized TSC1, promoted dissociation of the TSC complex from the lysosome, and eventually led to mTORC1 activation...
March 20, 2018: Cancer Research
Mohamed Rahmani, Jewel Nkwocha, Elisa Hawkins, Xinyan Pei, Rebecca E Parker, Maciej Kmieciak, Joel D Leverson, Deepak Sampath, Andrea Ferreira-Gonzalez, Steven Grant
Inhibitors targeting BCL-2 apoptotic proteins have significant potential for the treatment of acute myeloid leukemia (AML); however, complete responses are observed in only 20% of patients suggesting targeting BCL-2 alone is insufficient to yield durable responses. Here we assessed the efficacy of co-administration of the PI3K/mTOR inhibitor GDC-0980 or the p110β-sparing PI3K inhibitor taselisib with the selective BCL-2 antagonist venetoclax in AML cells. Tetracycline-inducible downregulation of BCL-2 significantly sensitized MV4-11 and MOLM-13 AML cells to PI3K inhibition...
March 20, 2018: Cancer Research
Manoj P Dandekar, Tao Peng, David D McPherson, Joao Quevedo, Jair C Soares, Shaoling Huang
AIM: Similar to ketamine, xenon gas acts as a glutamatergic N-methyl-d -aspartate receptor antagonist, but devoid of propensity to cause untoward effects. Herein, we loaded xenon gas into a liposomal carrier called xenon-containing liposomes (Xe-liposome) for systemic delivery, and investigated its effect as an antidepressant and also analyzed synaptic biomarkers including brain-derived neurotrophic factor (BDNF), protein kinase B (AKT), mammalian target of rapamycin (mTOR), protein kinase C (PKC) and extracellular signal-regulated kinase-1/2 (ERK1/2) in blood and brain...
March 17, 2018: Progress in Neuro-psychopharmacology & Biological Psychiatry
Jason Hellmann, Brian E Sansbury, Blenda Wong, Xiaofeng Li, Mansher Singh, Kristo Nuutila, Nan Chiang, Elof Eriksson, Charles N Serhan, Matthew Spite
Cutaneous injury causes underlying tissue damage that must be quickly repaired to minimize exposure to pathogens and to restore barrier function. While the role of growth factors in tissue repair is established, the role of lipid mediators in skin repair has not been extensively investigated. Using a mass spectrometry-based lipid mediator metabolomics approach, we identified D-series resolvins and related pro-resolving lipid mediators during skin injury in mice and pigs. Differentiation of human epidermal keratinocytes increased expression of 15-lipoxygenase and stereospecific production of 17S-hydroxydocosahexaenoic acid, the common upstream biosynthetic marker and precursor of D-series resolvins...
March 17, 2018: Journal of Investigative Dermatology
Fang Guo, Yong Zou, Yongjiang Zheng
Moracin M, a phenolic component obtained from Mori Cortex, has been reported to have anti-inflammatory activities. The present study was designed to investigate the effects and mechanisms of Moracin M on lipopolysaccharide (LPS)-treated nucleus pulposus cells (NPCs) in intervertebral disc. NPCs were treated with moracin M at different concentrations for 1 h and then stimulated with LPS (0.5 μg/mL) for 24 h. The result demonstrated that moracin M could significantly inhibit LPS-induced inflammation. The elevated levels of IL-1β, TNF-α and IL-6 induced by LPS could be reversed by moracin M in NPCs...
March 17, 2018: International Immunopharmacology
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