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R Jin, A Krasinskas, N-A Le, J V Konomi, J Holzberg, R Romero, M B Vos
BACKGROUND: Plasminogen activator inhibitor-1 (PAI-1) is the primary inhibitor of the endogenous fibrinolytic system and is known to be increased in obesity, insulin resistance and non-alcoholic fatty liver disease (NAFLD). We previously demonstrated that PAI-1 levels were closely related to the amount of hepatic steatosis in children. OBJECTIVES: The aim of this study was to characterize plasma PAI-1 in relationship to severity of inflammation and fibrosis, as well as to plasma lipids in children with NAFLD...
October 20, 2016: Pediatric Obesity
Elisabeth Waldmann, Georg Heinze, Arnulf Ferlitsch, Irina GessI, Daniela Sallinger, Philip Jeschek, Martha Britto-Arias, Petra Salzl, Elisabeth Fasching, Bernd Jilma, Michael Kundi, Michael Trauner, Monika Ferlitsch
BACKGROUND: Prevalence of (pre)cancerous colorectal lesions are higher in men than in women, although transition rates from advanced lesions to cancer is similar in both sexes. Our aim was to investigate whether the sex-specific difference in incidence of premalignant colorectal lesions might be explained by the impact of risk factors. METHODS: A cross-sectional study analysing health check-up examinations and screening colonoscopies performed within a national quality assurance program...
October 20, 2016: British Journal of Cancer
Yanbin Zhao, Wenbo Qiao, Xiaoyuan Wang, Hang Yin, Jianqi Cui, Yue Cui, Xuesong Chen, Jing Hu, Hailing Lu, Qingwei Meng, Yan Wang, Li Cai
14-3-3ζ is involved in tumor cell growth and apoptosis. However, the mechanism of 14-3-3ζ in lung squamous cell carcinoma (SCC) metastasis has not been illuminated. In our studies, we found that the expression of 14-3-3ζ was highly expressed in lung SCC compared to normal lung tissues. High expression of 14-3-3ζ was associated with pTNM stage (p<0.05) and lymph node metastasis (p<0.05). Furthermore, the expression of 14-3-3ζ protein was associated with high levels of TGFβR1 protein (p=0.005), and pSMAD3 (p=0...
October 15, 2016: Oncotarget
Kaijun Di, Naomi Lomeli, Spencer D Wood, Christopher D Vanderwal, Daniela A Bota
Mitochondrial dysfunction is a hallmark of cancer biology. Tumor mitochondrial metabolism is characterized by an abnormal ability to function in scarce oxygen conditions through glycolysis (the Warburg effect), and accumulation of mitochondrial DNA defects are present in both hereditary neoplasia and sporadic cancers. Mitochondrial Lon is a major regulator of mitochondrial metabolism and the mitochondrial response to free radical damage, and plays an essential role in the maintenance and repair of mitochondrial DNA...
October 15, 2016: Oncotarget
Yaoyao Shi, Yue Kuai, Lizhen Lei, Yuanyuan Weng, Friederike Berberich- Siebelt, Xinxia Zhang, Jinjie Wang, Yuan Zhou, Xin Jiang, Guoping Ren, Hongyang Pan, Zhengrong Mao, Ren Zhou
Dysregulation of the apoptotic pathway is widely recognized as a key step in lymphomagenesis. Notably, LITAF was initially identified as a p53-inducible gene, subsequently implicated as a tumor suppressor. Our previous study also showed LITAF to be methylated in 89.5% B-NHL samples. Conversely, deregulated expression of BCL6 is a pathogenic event in many lymphomas. Interestingly, our study found an oppositional expression of LITAF and BCL6 in B-NHL. In addition, LITAF was recently identified as a novel target gene of BCL6...
October 15, 2016: Oncotarget
Zhenze Zhao, Xiuye Ma, Spencer D Shelton, Derek C Sung, Monica Li, Daniel Hernandez, Maggie Zhang, Michael D Losiewiz, Yidong Chen, Alexander Pertsemlidis, Xiaojie Yu, Yuanhang Liu, Liqin Du
MYCN amplification is the most common genetic alteration in neuroblastoma and plays a critical role in neuroblastoma tumorigenesis. MYCN regulates neuroblastoma cell differentiation, which is one of the mechanisms underlying its oncogenic function. We recently identified a group of differentiation-inducing microRNAs. Given the demonstrated inter-regulation between MYCN and microRNAs, we speculated that MYCN and the differentiation-inducing microRNAs might form an interaction network to control the differentiation of neuroblastoma cells...
October 15, 2016: Oncotarget
Yuan Ren, Nan Ji, Xixiong Kang, Renzhi Wang, Wenbin Ma, Zhenjun Hu, Xingfeng Liu, Yajie Wang
Glioblastoma is a highly vascularized brain tumor that causes high mortality. Kininogen-1 (KNG1) has demonstrated both tumor suppressor and antiangiogenesis properties in gliobastoma cells. We analyzed the microarray and proteomic profiles of tumor tissues from glioblastoma patients (N = 180), and identified potential RNA regulators of the KNG1. Validation experiments in U87 glioblastoma cells showed that the regulation of KNG1 by CTU1, KIAA1274, and RAX was mediated by miR-138. The siRNA-mediated knockdown of CTU1, KIAA1274, or RAX in U87 cells and immortalized human endothelial cells (iHECs) significantly reduced KNG1 expression (P < 0...
October 14, 2016: Oncotarget
Yan-Ping Liu, Hui-Fang Zhu, Ding-Li Liu, Zhi-Yan Hu, Sheng-Nan Li, He-Ping Kan, Xiao-Yan Wang, Zu-Guo Li
Decoy receptor 3 (DcR3), a novel member of the tumor necrosis factor receptor (TNFR) family, was recently reported to be associated with tumorigenesis and metastasis. However, the role of DcR3 in human colorectal cancer (CRC) has not been fully elucidated. In this study, we found that DcR3 expression was significantly higher in human colorectal cancer tissues than in paired normal tissues, and that DcR3 expression was strongly correlated with tumor invasion, lymph node metastases and poor prognoses. Moreover, DcR3 overexpression significantly enhanced CRC cell proliferation and migration in vitro and tumorigenesis in vivo...
October 13, 2016: Oncotarget
Jiaxiong Lu, Shan Guan, Yanling Zhao, Yang Yu, Yongfeng Wang, Yonghua Shi, Xinfang Mao, Kristine L Yang, Wenjing Sun, Xin Xu, Joanna S Yi, Tianshu Yang, Jianhua Yang, Jed G Nuchtern
Neuroblastoma (NB), which accounts for about 15% of cancer-related mortality in children, is the most common childhood extracranial malignant tumor. In NB, somatic mutations of the tumor suppressor, p53, are exceedingly rare. Unlike in adult tumors, the majority of p53 downstream functions are still intact in NB cells with wild-type p53. Thus, restoring p53 function by blocking its interaction with p53 suppressors such as MDM2 is a viable therapeutic strategy for NB treatment. Herein, we show that MDM2 inhibitor SAR405838 is a potent therapeutic drug for NB...
October 13, 2016: Oncotarget
Tong Zhou, Luke Erber, Bing Liu, Yankun Gao, Hai-Bin Ruan, Yue Chen
Proline hydroxylation is a critical cellular mechanism regulating oxygen-response pathways in tumor initiation and progression. Yet, its substrate diversity and functions remain largely unknown. Here, we report a system-wide analysis to characterize proline hydroxylation substrates in cancer cells using an immunoaffinity-purification assisted proteomics strategy. We identified 562 sites from 272 proteins in HeLa cells. Bioinformatic analysis revealed that proline hydroxylation substrates are significantly enriched with mRNA processing and stress-response cellular pathways with canonical and diverse flanking sequence motifs...
October 13, 2016: Oncotarget
Lujun Chen, Quanqin Xie, Zhigang Wang, Liangrong Shi, Changping Wu, Jingting Jiang
The co-stimulatory ligands of B7-family have been confirmed to play an important role in negatively regulating the T-cell mediated anti-tumor immunity. In addition, these inhibitory molecules are also aberrantly expressed on various human cancers tissues, and significantly associated with cancer progression and patients' poor prognoses. We have previously reported that B7-H3 and B7-H4 ligands are highly expressed in human esophageal cancer tissues. Herein, we tried to further analyze the value of their combined expression on prognostic prediction for esophageal cancer patients...
October 13, 2016: Oncotarget
Yu-Chuan Huang, Chung-Ta Lee, Jenq-Chang Lee, Yao-Wen Liu, Ying-Jen Chen, Joseph T Tseng, Jui-Wen Kang, Bor-Shyang Sheu, Bo-Wen Lin, Liang-Yi Hung
MicorRNA-137 is silenced in human colorectal cancer tissues and colon polyps. Our study showed that the decreased expression of miR-137 is significantly different in various types of polyp which maintain different potentials to lead to CRC development. The expression of miR-137 gradually decreases during the process of colorectal carcinogenesis. Receiver operating characteristic curve (ROC) analysis indicates that the loss of miR-137 expression in colon polyps can serve as a biomarker to predict the predisposition of colorectal carcinogenesis...
October 18, 2016: Oncotarget
Maryam Dastan, Nowruz Najafzadeh, Ali Abedelahi, Mohammadreza Sarvi, Ali Niapour
Minoxidil and human platelet lysate (HPL) are commonly used to treat patients with hair loss. However, the roles of HPL versus minoxidil in hair follicle biology largely remain unknown. Here, we hypothesized that bulge and dermal papilla (DP) cells may express specific genes, including Kras, Erk, Akt, Shh and β-catenin after exposure to minoxidil or HPL. The mouse hair follicles were isolated on day 10 after depilation and bulge or DP regions were dissected. The bulge and DP cells were cultured for 14days in DMEM/F12 medium...
October 17, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Siroon Bekkering, Inge van den Munckhof, Tim Nielen, Evert Lamfers, Charles Dinarello, Joost Rutten, Jacqueline de Graaf, Leo A B Joosten, Mihai G Netea, Marc E R Gomes, Niels P Riksen
BACKGROUND AND AIMS: We have recently reported that monocytes can undergo functional and transcriptional reprogramming towards a long-term pro-inflammatory phenotype after brief in vitro exposure to atherogenic stimuli such as oxidized LDL. This process is termed 'trained immunity', and is mediated by epigenetic remodeling and a metabolic switch towards increased aerobic glycolysis. We hypothesize that trained immunity contributes to atherogenesis. Therefore, we investigated the inflammatory phenotype and epigenetic remodeling of monocytes from patients with and without established atherosclerosis...
October 12, 2016: Atherosclerosis
James P Strassner, John E Harris
Vitiligo is an autoimmune disease of the skin that leads to life-altering depigmentation and remains difficult to treat. However, clinical observations and translational studies over 30-40 years have led to the development of an insightful working model of disease pathogenesis: Genetic risk spanning both immune and melanocyte functions is pushed over a threshold by known and suspected environmental factors to initiate autoimmune T cell-mediated killing of melanocytes. While under cellular stress, melanocytes appear to signal innate immunity to activate T cells...
October 17, 2016: Current Opinion in Immunology
Elżbieta Lorenc-Koci, Anna Czarnecka, Kinga Kamińska, Joanna Knutelska, Małgorzata Zygmunt, Magdalena Dudek
BACKGROUND: Interaction between dopaminergic and nitrergic neurotransmission in the brain plays a crucial role in the control of motor function and in the regulation of blood pressure (BP). In Parkinson's disease (PD), dopaminergic denervation of the striatum leads to disturbances in the nitrergic system in the basal ganglia. Recently, it has been demonstrated that addition of a low dose of the nitric oxide donor molsidomine to l-DOPA therapy improves dopaminergic neurotransmission in the denervated nigrostriatal system and weakens dyskinesias in rodent models of the disease...
September 28, 2016: Pharmacological Reports: PR
Sergio Valbuena, Juan Lerma
Neurotransmitter receptors are responsible for the transfer of information across the synapse. While ionotropic receptors form ion channels and mediate rapid membrane depolarization, so-called metabotropic receptors exert their action though slower, less direct intracellular signaling pathways. Glutamate, GABA, and acetylcholine can activate both ionotropic and metabotropic receptors, yet the distinction between these "canonical" signaling systems has become less clear since ionotropic receptors were proposed to also activate second messenger systems, defining a "non-canonical" signaling pathway...
October 19, 2016: Neuron
Ya-Qin Tan, Jing Zhang, Gang Zhou
Macroautophagy/autophagy is a conserved lysosomal degradation process essential for cell physiology and human health. By regulating apoptosis, inflammation, pathogen clearance, immune response and other cellular processes, autophagy acts as a modulator of pathogenesis and is a potential therapeutic target in diverse diseases. With regard to oral disease, autophagy can be problematic either when it is activated or impaired, because this process is involved in diverse functions, depending on the specific disease and its level of progression...
October 20, 2016: Autophagy
Indu Jose Thoompumkal, Krishnan Rehna, Kumaraswamy Anbarasu, Sundarasamy Mahalingam
Guanine nucleotide binding protein-like 3-like (GNL3L) is an evolutionarily conserved putative nucleolar GTPase belonging to the HSR1-MMR1 family. In the present study, using protein-protein interaction assays, we show that Leucine Zipper Down-regulated in Cancer-1 (LDOC1) is a novel interacting partner of GNL3L. Furthermore, our results reveal that ectopic expression of LDOC1 destabilizes endogenous GNL3L levels and down modulates GNL3L-induced cell proliferation, in contrast, the knockdown of LDOC1 potentiates cell proliferation upon GNL3L expression...
October 20, 2016: Cell Cycle
Zuriñe Antón, Ane Landajuela, Javier H Hervás, L Ruth Montes, Sonia Hernández-Tiedra, Guillermo Velasco, Felix M Goñi, Alicia Alonso
The phospholipid cardiolipin (CL) has been proposed to play a role in selective mitochondrial autophagy, or mitophagy. CL externalization to the outer mitochondrial membrane would act as a signal for the human Atg8 ortholog subfamily, MAP1LC3 (LC3). The latter would mediate both mitochondrial recognition and autophagosome formation, ultimately leading to removal of damaged mitochondria. We have applied quantitative biophysical techniques to the study of CL interaction with various Atg8 human orthologs, namely LC3B, GABARAPL2 and GABARAP...
October 20, 2016: Autophagy
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