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Ingenuity pathway analysis

Peisheng Liang, Wangyong Zhu, Tianjun Lan, Qian Tao
Saliva secretion disorder is one of the most common symptoms in primary Sjögren syndrome (pSS). Salivary biomarkers related to saliva secretion disorder were identified in a pSS murine model, NOD/ShiLtJ mouse, using differential proteomic analysis. Candidate biomarkers were screened with Kyoto Encyclopedia of Genes and Genomes pathway analysis and validated in saliva and salivary glands by western blotting and immunohistochemistry (IHC). Biological functions were detected using ingenuity pathway analysis (IPA)...
March 12, 2018: Journal of Pharmaceutical and Biomedical Analysis
Zsolt Zador, Andrew T King, Nophar Geifman
BACKGROUND: Atypical meningiomas are common central nervous system neoplasms with high recurrence rate and poorer prognosis compared to their grade I counterparts. Surgical excision and radiotherapy remains the mainstay therapy but medical treatments are limited. We explore new drug candidates using computational drug repurposing based on the gene expression signature of atypical meningioma tissue with subsequent analysis of drug-generated expression profiles. We further explore possible mechanisms of action for the identified drug candidates using ingenuity pathway analysis (IPA)...
2018: PloS One
Nuray Erin, Nur Ogan, Azmi Yerlikaya
PURPOSE: Metastatic breast cancer is resistant to many conventional treatments and novel therapeutic targets are needed. We previously isolated subsets of 4T1 murine breast cancer cells which metastasized to liver (4TLM), brain (4TBM), and heart (4THM). Among these cells, 4TLM is the most aggressive one, demonstrating mesenchymal phenotype. Here we compared secreted proteins from 4TLM, 4TBM, and 4THM cells and compared with that of hardly metastatic 67NR cells to detect differentially secreted factors involved in organ-specific metastasis...
March 20, 2018: Breast Cancer Research and Treatment
Michael Lehrer, Anindya Bhadra, Sathvik Aithala, Visweswaran Ravikumar, Youyun Zheng, Basak Dogan, Emerlinda Bonaccio, Elizabeth S Burnside, Elizabeth Morris, Elizabeth Sutton, Gary J Whitman, Jose Net, Kathy Brandt, Marie Ganott, Margarita Zuley, Arvind Rao
Background: Imaging features derived from MRI scans can be used for not only breast cancer detection and measuring disease extent, but can also determine gene expression and patient outcomes. The relationships between imaging features, gene/protein expression, and response to therapy hold potential to guide personalized medicine. We aim to characterize the relationship between radiologist-annotated tumor phenotypic features (based on MRI) and the underlying biological processes (based on proteomic profiling) in the tumor...
January 2018: Oncoscience
Raffaele Altara, Fouad A Zouein, Rita Dias Brandão, Saeed N Bajestani, Alessandro Cataliotti, George W Booz
Standard therapies for heart failure with preserved ejection fraction (HFpEF) have been unsuccessful, demonstrating that the contribution of the underlying diastolic dysfunction pathophysiology differs from that of systolic dysfunction in heart failure and currently is far from being understood. Complicating the investigation of HFpEF is the contribution of several comorbidities. Here, we selected three established rat models of diastolic dysfunction defined by three major risk factors associated with HFpEF and researched their commonalities and differences...
2018: Frontiers in Cardiovascular Medicine
Shu Yang, Zhihua Xing, Tao Liu, Jing Zhou, Qinghua Liang, Tao Tang, Hanjin Cui, Weijun Peng, Xingui Xiong, Yang Wang
Background: Rheumatoid arthritis (RA) is a common worldwide public health problem, which causes a chronic, systemic inflammatory disorder of synovial joints. Paeoniflorin (PA) has achieved positive results to some extent for the treatment of RA. Purpose: This study aimed to reveal the potential druggable targets of PA in an experimental RA model using quantitative proteomics analysis. Study design and methods: Thirty Sprague-Dawley rats were randomly divided into a normal group, model group and PA group...
2018: Drug Design, Development and Therapy
Chun-Fu Hong, Ying-Chen Chen, Wei-Chun Chen, Keng-Chang Tu, Meng-Hsiun Tsai, Yung-Kuan Chan, Shyr Shen Yu
A microarray analysis generally contains expression data of thousands of genes, but most of them are irrelevant to the disease of interest, making analyzing the genes concerning specific diseases complicated. Therefore, filtering out a few essential genes as well as their regulatory networks is critical, and a disease can be easily diagnosed just depending on the expression profiles of a few critical genes. In this study, a target gene screening (TGS) system, which is a microarray-based information system that integrates F-statistics, pattern recognition matching, a two-layer K-means classifier, a Parameter Detection Genetic Algorithm (PDGA), a genetic-based gene selector (GBG selector) and the association rule, was developed to screen out a small subset of genes that can discriminate malignant stages of cancers...
March 14, 2018: Journal of Biomedical Informatics
Jaana Rysä, Heikki Tokola, Heikki Ruskoaho
Mechanical forces are able to activate hypertrophic growth of cardiomyocytes in the overloaded myocardium. However, the transcriptional profiles triggered by mechanical stretch in cardiac myocytes are not fully understood. Here, we performed the first genome-wide time series study of gene expression changes in stretched cultured neonatal rat ventricular myocytes (NRVM)s, resulting in 205, 579, 737, 621, and 1542 differentially expressed (>2-fold, P < 0.05) genes in response to 1, 4, 12, 24, and 48 hours of cyclic mechanical stretch...
March 16, 2018: Scientific Reports
Mona Dawood, Sami Hamdoun, Thomas Efferth
Arsenic trioxide is a traditional remedy in Chinese Medicine since ages. Nowadays, it is clinically used to treat acute promyelocytic leukemia (APL) by targeting PML/RARA. However, the drug's activity is broader and the mechanisms of action in other tumor types remain unclear. In this study, we investigated molecular modes of action by classical and network pharmacological approaches. CEM/ADR5000 resistance leukemic cells were similar sensitive to As2 O3 as their wild-type counterpart CCRF-CEM (resistance ratio: 1...
2018: Frontiers in Pharmacology
Guohong Liu, Francois X Claret, Fuling Zhou, Yunbao Pan
C-Jun activation domain-binding protein-1 (Jab1) involves in controlling cellular proliferation, cell cycle, apoptosis, affecting a series of pathways, as well as regulating genomic instability and DNA damage response (DDR). Jab1/COPS5 dysregulation contributes to oncogenesis by deactivating several tumor suppressors and activating oncogenes. Jab1 overexpression was found in many tumor types, illuminating its important role in cancer initiation, progression, and prognosis. Jab1/COPS5 has spurred a strong research interest in developing inhibitors of oncogenes/oncoproteins for cancer therapy...
2018: Frontiers in Pharmacology
Yara Suliman, Frank Becker, Klaus Wimmers
Poor fertility of breeding stallions is a recognised problem in the equine industry. The aim of the present study was to detect molecular pathways using two groups of stallions that differed in pregnancy rates as well as in the proportion of normal and motile spermatozoa. RNA was isolated from spermatozoa of each stallion and microarray data were analysed to obtain a list of genes for which transcript abundance differed between the groups (P ≤0.05, fold change ≥1.2). In all, there were 437 differentially expressed (DE) genes between the two groups (P ≤ 0...
March 14, 2018: Reproduction, Fertility, and Development
Philipp Strauss, Hans-Peter Marti, Christian Beisland, Andreas Scherer, Vegard Lysne, Sabine Leh, Arnar Flatberg, Even Koch, Vidar Beisvag, Lea Landolt, Trude Skogstrand, Øystein Eikrem
Novel predictive tools for clear cell renal cell carcinoma (ccRCC) are urgently needed. MicroRNAs (miRNAs) have been increasingly investigated for their predictive value, and formalin-fixed paraffin-embedded biopsy archives may potentially be a valuable source of miRNA sequencing material, as they remain an underused resource. Core biopsies of both cancerous and adjacent normal tissues were obtained from patients ( n = 12) undergoing nephrectomy. After small RNA-seq, several analyses were performed, including classifier evaluation, obesity-related inquiries, survival analysis using publicly available datasets, comparisons to the current literature and ingenuity pathway analyses...
March 10, 2018: International Journal of Molecular Sciences
Ivan Hernandez, Jonathan M Baio, Eric Tsay, Aida F Martinez, Tania I Fuentes, Leonard L Bailey, Nahidh W Hasaniya, Mary Kearns-Jonker
The use of cardiovascular progenitor cells (CPCs) to repair damaged myocardium has been the focus of intense research. Previous reports have shown that pretreatments, including hypoxia, improve cell function. However, the age-dependent effects of short-term hypoxia on CPCs, and the role of signaling in these effects, are unknown. Cloned neonatal and adult CPCs expressing Isl1, c-Kit, KDR, PDGFRA, and CXCR4, were preconditioned using hypoxia (1% O2 for six hours). Intracellular signaling pathway changes were modeled using Ingenuity Pathway Analysis (IPA), while qRT-PCR, flow cytometry, and immunoblotting were used to measure pathway activation...
2018: American Journal of Stem Cells
Mindi Zhao, Jianqiang Wu, Xundou Li, Youhe Gao
Urine is a better source than plasma for biomarker studies, as it can accumulate all changes in the body. Various candidate urinary biomarkers of physiological condition, kidney disease and even brain dysfunction, have been detected in urine; however, urine has rarely been used to reflect cardiac diseases. In this study, urine at day 0, 14, 21 and 28 were collected from the myosin-induced autoimmune myocarditis rat models. The candidate urinary biomarkers were then characterized using the isobaric tandem mass tag labeling approach coupled with offline two-dimensional reverse-phase liquid chromatography and high-resolution mass spectrometry...
March 7, 2018: Journal of Proteomics
Mana Ogawa, Toshitada Nagai, Yoshikazu Saito, Hitonari Miyaguchi, Kei Kumakura, Keiko Abe, Tomiko Asakura
Mastication enhances brain function and mental health, but little is known about the molecular mechanisms underlying the effects of mastication on neural development in early childhood. Therefore, we analysed the gene expression in juvenile neural circuits in rats fed with a soft or chow diet immediately after weaning. We observed that the gene expression patterns in the thalamus varied depending on the diet. Furthermore, gene ontology analysis revealed that two terms were significantly enhanced: chemical synaptic transmission and positive regulation of dendritic spine morphogenesis...
March 7, 2018: Biochemical and Biophysical Research Communications
Haiqiang Yao, Shanlan Mo, Ji Wang, Yingshuai Li, Chong-Zhi Wang, Jin-Yi Wan, Zengliang Zhang, Yu Chen, Ranran Sun, Chun-Su Yuan, Xin Liu, Lingru Li, Qi Wang
BACKGROUND/AIMS: Metabolic diseases are leading health concerns in today's global society. In traditional Chinese medicine (TCM), one body type studied is the phlegm-dampness constitution (PC), which predisposes individuals to complex metabolic disorders. Genomic studies have revealed the potential metabolic disorders and the molecular features of PC. The role of epigenetics in the regulation of PC, however, is unknown. METHODS: We analyzed a genome-wide DNA methylation in 12 volunteers using Illumina Infinium Human Methylation450 BeadChip on peripheral blood mononuclear cells (PBMCs)...
March 2, 2018: Cellular Physiology and Biochemistry
Dingyuan Hu, Daniel Ansari, Krzysztof Pawłowski, Qimin Zhou, Agata Sasor, Charlotte Welinder, Theresa Kristl, Monika Bauden, Melinda Rezeli, Yi Jiang, György Marko-Varga, Roland Andersson
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy. Here we show that shotgun and targeted protein sequencing can be used to identify potential prognostic biomarkers in formalin-fixed paraffin-embedded specimens from 9 patients with PDAC with "short" survival (<12 months) and 10 patients with "long" survival (>45 months) undergoing surgical resection. A total of 24 and 147 proteins were significantly upregulated [fold change ≥2 or ≤0.5 and P<0.05; or different detection frequencies (≥5 samples)] in patients with "short" survival (including GLUT1) and "long" survival (including C9orf64, FAM96A, CDH1 and CDH17), respectively...
February 9, 2018: Oncotarget
Brian D Adams, Hannah Arem, Monica J Hubal, Brenda Cartmel, Fangyong Li, Maura Harrigan, Tara Sanft, Christopher J Cheng, Lajos Pusztai, Melinda L Irwin
PURPOSE: Obesity and weight gain are associated with comorbidities including a higher risk of tumor recurrence and cancer-related deaths among breast cancer (BC) survivors; however, the underlying mechanisms linking obesity and cancer are poorly understood. Given the lack of clinically validated BC biomarkers, obesity and weight-loss studies utilize serum biomarkers as the intermediary outcomes of tumor recurrence. Studies have indicated microRNAs (miRNA)s are reliable biomarkers for cancer...
March 6, 2018: Breast Cancer Research and Treatment
Aneta Stefanidis, Nicole M Wiedmann, Sonika Tyagi, Andrew M Allen, Matthew J Watt, Brian J Oldfield
OBJECTIVE: The potential for brown adipose tissue (BAT) to be targeted as a therapeutic option to combat obesity has been heightened by the discovery of a brown-like form of inducible "beige" adipose tissue in white fat which has overlapping structural and functional properties to "classical" BAT. The likelihood that both beige and brown fat are recruited functionally by neural mechanisms, taken together with the lack of a detailed understanding of the nature of changes in the nervous system when white adipose tissue (WAT) is transformed to brown, provides the impetus for this study...
February 10, 2018: Molecular Metabolism
Xavier Vidal-Gómez, Daniel Pérez-Cremades, Ana Mompeón, Ana Paula Dantas, Susana Novella, Carlos Hermenegildo
BACKGROUND/AIMS: Estrogen signalling plays an important role in vascular biology as it modulates vasoactive and metabolic pathways in endothelial cells. Growing evidence has also established microRNA (miRNA) as key regulators of endothelial function. Nonetheless, the role of estrogen regulation on miRNA profile in endothelial cells is poorly understood. In this study, we aimed to determine how estrogen modulates miRNA profile in human endothelial cells and to explore the role of the different estrogen receptors (ERα, ERβ and GPER) in the regulation of miRNA expression by estrogen...
February 28, 2018: Cellular Physiology and Biochemistry
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