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Ingenuity pathway analysis

Hongtao Guo, Xuyan Niu, Yan Gu, Cheng Lu, Cheng Xiao, Kevin Yue, Ge Zhang, Xiaohua Pan, Miao Jiang, Yong Tan, Hongwei Kong, Zhenli Liu, Guowang Xu, Aiping Lu
Pattern classification is a key approach in Traditional Chinese Medicine (TCM), and it is used to classify the patients for intervention selection accordingly. TCM cold and heat patterns, two main patterns of rheumatoid arthritis (RA) had been explored with systems biology approaches. Different regulations of apoptosis were found to be involved in cold and heat classification in our previous works. For this study, the metabolic profiling of plasma was explored in RA patients with typical TCM cold or heat patterns by integrating liquid chromatography/mass spectrometry (LC/MS) and gas chromatography/mass spectrometry (GC/MS) platforms in conjunction with the Ingenuity Pathway Analysis (IPA) software...
October 21, 2016: International Journal of Molecular Sciences
John J Guardiola, Juliane I Beier, K Cameron Falkner, Benjamin Wheeler, Craig James McClain, Matt Cave
BACKGROUND: Occupational vinyl chloride (VC) exposures have been associated with toxicant-associated steatohepatitis and liver cancer. Metabolomics has been used to clarify mode of action in drug-induced liver injury but has not been performed following VC exposures. METHODS: Plasma samples from 17 highly exposed VC workers without liver cancer and 27 unexposed healthy volunteers were obtained for metabolite extraction and GC/MS and LC/MS(2) analysis. Following ion identification/quantification, Ingenuity pathway analysis was performed...
October 17, 2016: Toxicology and Applied Pharmacology
Ryan D Sheldon, Kayla M Kanosky, Kevin D Wells, Lili Miles, James W Perfield, Stavra Xanthakos, Thomas H Inge, R Scott Rector
BACKGROUND: Mechanisms responsible for progression of nonalcoholic fatty liver disease (NAFLD) to steatohepatitis (NASH) remain poorly defined. METHODS: To examine the potential contribution of adipose tissue to NAFLD progression, we performed a complete transcriptomic analysis using RNA-sequencing (RNA-seq) on intra-abdominal adipose tissue (IAT) from severely obese adolescents (Mage 16.9±0.4 yrs; BMI z-score 2.7±0.1) undergoing bariatric surgery and liver biopsy categorized into 3 groups; No steatosis (Normal, n=8), steatosis only (n=13), or NASH (n=10) by liver histology...
October 7, 2016: Physiological Genomics
Mathieu Fonteneau, Dominique Filliol, Patrick Anglard, Katia Befort, Pascal Romieu, Jean Zwiller
DNA methylation is a major epigenetic process which regulates the accessibility of genes to the transcriptional machinery. In the present study, we investigated whether modifying the global DNA methylation pattern in the brain would alter cocaine intake by rats, using the cocaine self-administration test. The data indicate that treatment of rats with the DNA methyltransferase inhibitors 5-aza-2'-deoxycytidine and zebularine actually enhanced the reinforcing properties of cocaine. To get some insights about the underlying neurobiological mechanisms, a genome-wide methylation analysis was undertaken in the prefrontal cortex of rats self-administering cocaine and treated or not with 5-aza-2'-deoxycytidine...
October 20, 2016: Genes, Brain, and Behavior
Dawid Walas, Karol Nowicki-Osuch, Dominic Alibhai, Julian Paton
OBJECTIVE: Cerebrovascular remodeling in the SHR may be causative to the known brainstem hypoperfusion. Using RNA sequencing, we examined age-related processes that may govern remodeling of the cerebral arteries in the SHR. DESIGN AND METHOD: In SHR and their progenitor (normotensive) control (Wistar Kyoto, WKY), RNA-seq was performed at three ages: 5, 9, 13 weeks old. Cerebral arteries were flushed and peeled off the brain, stripped of meninges, snap frozen and RNA extracted...
September 2016: Journal of Hypertension
Francesca Bianchi, Michele Sommariva, Loris De Cecco, Tiziana Triulzi, Sandra Romero-Cordoba, Elda Tagliabue, Lucia Sfondrini, Andrea Balsari
The autoimmune regulator gene (AIRE) plays a fundamental role in tolerance by promoting the expression of tissue-specific antigens in medullary thymic epithelial cells (mTECs). Recently, AIRE expression was detected also in human keratinocytes and in tumors originating in stratified epithelia. Here, we tested whether AIRE is expressed in cancer cells. We analyzed AIRE expression in cancer cases from The Cancer Genome Atlas (TCGA) RNA-seq dataset and we found association with better outcome. AIRE protein expression was verified by immunohistochemistry in a cohort of 39 human breast cancer specimens and its prognostic relevance was confirmed in microarray-based gene expression dataset NKI-295 and KM-Plotter...
October 18, 2016: Cell Cycle
Hjalte C R Sass, Rehannah Borup, Mikkel Alanin, Finn Cilius Nielsen, Per Cayé-Thomasen
The objective of this study was to determine global gene expression in relation to Vestibular schwannomas (VS) growth rate and to identify signal transduction pathways and functional molecular networks associated with growth. Repeated magnetic resonance imaging (MRI) prior to surgery determined tumor growth rate. Following tissue sampling during surgery, mRNA was extracted from 16 sporadic VS. Double stranded cDNA was synthesized from the mRNA and used as template for in vitro transcription reaction to synthesize biotin-labeled antisense cRNA, which was hybridized to Affymetrix HG-U133A arrays and analyzed by dChip software...
October 17, 2016: Journal of Neuro-oncology
Enrique Jurado-Ruiz, Lourdes M Varela, Amparo Luque, Genoveva Berná, Gladys Cahuana, Enrique Martinez-Force, Rocío Gallego-Durán, Bernat Soria, Baukje de Roos, Manuel Romero Gómez, Franz Martín
SCOPE: We evaluated the protective effect of extra virgin olive oil (EVOO) in high-fat diets (HFDs) on the inflammatory response and liver damage in a non-alcoholic fatty liver disease (NAFLD) mouse model. METHODS AND RESULTS: C57BL/6J mice fed a standard diet or a lard-based HFD (HFD-L) for 12 weeks to develop NAFLD. HFD fed mice were then divided into four groups and fed for 24 weeks with: HFD-L; HFD-EVOO; HFD-OL (phenolics-rich EVOO) and R (reversion; standard diet)...
October 17, 2016: Molecular Nutrition & Food Research
Paulina Płoszaj, Andrzej Regiec, Stanisław Ryng, Agnieszka Piwowar, Marian L Kruzel
The 5-amino-3-methyl-4-isoxazolecarboxylic acid hydrazide (HIX) is a synthetic isoxazole derivative with a potential for development as an anti-inflammatory drug candidate. The goal of this study was to explore in vitro autoimmune and inflammatory gene modulation by HIX in human Caco-2 cultured cells. The effect of low dose of HIX was tested on the expression level of RNA in 24h Caco-2 cultures using the QIAGEN Th17 for Autoimmunity & Inflammation RT(2) Profiler PCR Array. We choose the PCR technology as the most reliable and sensitive gene expression profiling method for analyzing specific gene regulatory networks...
October 17, 2016: Immunopharmacology and Immunotoxicology
L Dioni, S Sucato, V Motta, S Iodice, L Angelici, C Favero, T Cavalleri, L Vigna, B Albetti, S Fustinoni, P Bertazzi, A Pesatori, V Bollati
BACKGROUND/OBJECTIVES: Epidemiological studies suggest a link between chromium (Cr) status and cardiovascular disease. Increased urinary excretion of Cr was reported in subjects with diabetes compared with non-diabetic controls and those with non-diabetic insulin resistance. Epigenetic alterations have been linked to the presence of Cr, and microRNA (miRNA) expression has been implicated in the pathogenesis of metabolic diseases and cardiovascular diseases (CVDs). We investigated the association between Cr excretion and miRNA expression in leukocytes from obese subjects...
October 12, 2016: European Journal of Clinical Nutrition
Mijeong Park, Mark J Raftery, Paul S Thomas, Carolyn L Geczy, Katherine Bryant, Nicodemus Tedla
FcγRI cross-linking on monocytes may trigger clathrin-mediated endocytosis, likely through interaction of multiple intracellular molecules that are controlled by phosphorylation and dephosphorylation events. However, the identity of phospho-proteins and their regulation are unknown. We proposed the leukocyte immunoglobulin-like receptor B4 (LILRB4) that inhibits FcγRI-mediated cytokine production via Tyr dephosphorylation of multiple kinases, may also regulate endocytosis/phagocytosis through similar mechanisms...
October 11, 2016: Scientific Reports
Y Zhang, E J Crofton, X Fan, D Li, F Kong, M Sinha, B A Luxon, H M Spratt, C F Lichti, T A Green
Transcriptomic and proteomic approaches have separately proven effective at identifying novel mechanisms affecting addiction-related behavior; however, it is difficult to prioritize the many promising leads from each approach. A convergent secondary analysis of proteomic and transcriptomic results can glean additional information to help prioritize promising leads. The current study is a secondary analysis of the convergence of recently published separate transcriptomic and proteomic analyses of nucleus accumbens (NAc) tissue from rats subjected to environmental enrichment vs...
October 4, 2016: Neuroscience
Donatella Aiello, Francesca Casadonte, Rosa Terracciano, Rocco Damiano, Rocco Savino, Giovanni Sindona, Anna Napoli
Prostate cancer (PCa) is the sixth highest causes of cancer-related deaths in men. The molecular events underlying its behavior and evolution are not completely understood. Prostate-specific antigen (PSA) is the only approved Food and Drug Administration biomarker. A panel of ten stage-specific tumoral and adjacent non tumoral tissues from patients affected by PCa (Gleason score 6, 3+3; PSA 10 ÷19 ng/ml) was investigated by MS-based proteomics approach. The proposed method was based on identifying the base-soluble proteins from tissue, established an efficient study, which lead to a deeper molecular perspective understanding of the PCa...
2016: Oncoscience
Tsan-Wan Chiu, Ying-Lun Chen, Chien-Yi Wu, Pei-Ling Yu, Ying-Hua Shieh, Bin Huang
BACKGROUND: Hydrogen sulfide (H2S) is one of the endogenous gaseous molecules promoting the production of nitric oxide (NO) which has cardioprotective functions. However, the role of the H2S-mediated protein S-nitrosoproteome and its subsequent physiological response remains unclear. METHODS: Endothelial cells EAhy 926 were treated with 50 μM of H2S for 2 hours. The NO bound S-nitrosoproteins were purified by a biotin-switch and then digested by trypsin. Resulting peptides from control and H2S treatment were separately labeled by isobaric tag for relative and absolute quantitation 114/115, quantified by liquid chromatography tandem-mass spectrometry and analyzed by ingenuity pathway analysis (IPA) software...
September 2016: Acta Cardiol Sin
Atsushi Kiba, Kouji Banno, Megumi Yanokura, Mari Asada, Yusuke Nakayama, Daisuke Aoki, Tatsuya Watanabe
AIM: Micro ribonucleic acids (miRNAs) play an important pathological role in endometriosis. Leuprolide acetate, an analog of gonadotropin-releasing hormone, is widely used to treat endometriosis; however, the molecular mechanisms involved in endometriotic tissue regression remain unclear. We performed miRNA expression profiling of clinical ovarian endometrioma to obtain insight into the effects of leuprolide acetate treatment. METHODS: We obtained clinical samples from nine normal eutopic endometrium, eight ovarian endometriotic, and 12 leuprolide acetate-treated endometriotic tissues...
October 6, 2016: Journal of Obstetrics and Gynaecology Research
Fan Yi, Xiao-Lei Tan, Xin Yan, Hai-Bo Liu
BACKGROUND: Lepidium meyenii Walpers (maca) is an herb known as a traditional nutritional supplement and widely used in Peru, North America, and Europe to enhance human fertility and treat osteoporosis. The secondary metabolites of maca, namely, maca alkaloids, macaenes, and macamides, are bioactive compounds, but their targets are undefined. METHODS: The pharmacophore-based PharmaDB targets database screening joint the ligand shape similarity-based WEGA validation approach is proposed to predict the targets of these unique constituents and was performed using Discovery Studio 4...
2016: Chinese Medicine
Yang Wang, Zhi-Hao Huang, Yang-Jia Li, Gui-Wei He, Ru-Yuan Yu, Jie Yang, Wan-Ting Liu, Bin Li, Qing-Yu He
Emerging evidence suggested that necroptosis has essential functions in many human inflammatory diseases, but the molecular mechanisms of necroptosis remain unclear. Here, we employed SILAC quantitatively dynamic proteomics to compare the protein changes during TNF-α-induced necroptosis at different time points in murine fibrosarcoma L929 cells with caspase-8 deficiency, and then performed the systematical analysis on the signaling networks involved in the progress using bioinformatics methods. Our results showed that a total of 329, 421 and 378 differentially expressed proteins were detected at three stages of necroptosis, respectively...
October 4, 2016: Apoptosis: An International Journal on Programmed Cell Death
Tao Su, Yong Tan, Man-Shan Tsui, Hua Yi, Xiu-Qiong Fu, Ting Li, Chi Leung Chan, Hui Guo, Ya-Xi Li, Pei-Li Zhu, Anfernee Kai Wing Tse, Hui Cao, Ai-Ping Lu, Zhi-Ling Yu
Pinelliae Rhizoma (PR) is a commonly used Chinese medicinal herb, but it has been frequently reported about its toxicity. According to the traditional Chinese medicine theory, processing can reduce the toxicity of the herbs. Here, we aim to determine if processing reduces the toxicity of raw PR, and to explore the underlying mechanisms of raw PR-induced toxicities and the toxicity-reducing effect of processing. Biochemical and histopathological approaches were used to evaluate the toxicities of raw and processed PR...
October 4, 2016: Scientific Reports
Sarah M Romereim, Adam F Summers, William E Pohlmeier, Pan Zhang, Xiaoying Hou, Heather A Talbott, Robert A Cushman, Jennifer R Wood, John S Davis, Andrea S Cupp
After ovulation, somatic cells of the ovarian follicle (theca and granulosa cells) become the small and large luteal cells of the corpus luteum. Aside from known cell type-specific receptors and steroidogenic enzymes, little is known about the differences in the gene expression profiles of these four cell types. Analysis of the RNA present in each bovine cell type using Affymetrix microarrays yielded new cell-specific genetic markers, functional insight into the behavior of each cell type via Gene Ontology Annotations and Ingenuity Pathway Analysis, and evidence of small and large luteal cell lineages using Principle Component Analysis...
September 28, 2016: Molecular and Cellular Endocrinology
Ramani Soundararajan, Timothy M Stearns, Alexander Czachor, Jutaro Fukumoto, Christina Turn, Emma Westermann-Clark, Mason Breitzig, Lee Tan, Richard F Lockey, Benjamin L King, Narasaiah Kolliputi
OBJECTIVE: Recent studies implicate cardiolipin oxidation in several age-related diseases. Atp8b1 encoding Type 4 P-type ATPases is a cardiolipin transporter. Mutation in Atp8b1 gene or inflammation of the lungs impairs the capacity of Atp8b1 to clear cardiolipin from lung fluid. However, the link between Atp8b1 mutation and age-related gene alteration is unknown. Therefore, we investigated how Atp8b1 mutation alters age-related genes. METHODS: We performed Affymetrix gene profiling of lungs isolated from young (7-9 wks, n=6) and aged (14 months, 14 M, n=6) C57BL/6 and Atp8b1 mutant mice...
September 29, 2016: Aging
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