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Kyosuke Yamanishi, Keiichiro Mukai, Takuya Hashimoto, Kaoru Ikubo, Keiji Nakasho, Yosif El-Darawish, Wen Li, Daisuke Okuzaki, Yuko Watanabe, Tetsu Hayakawa, Hiroshi Nojima, Hiromichi Yamanishi, Haruki Okamura, Hisato Matsunaga
BACKGROUND: The cytokine interleukin-18 was originally identified as an interferon-γ-inducing proinflammatory factor; however, there is increasing evidence to suggest that it has non-immunological effects on physiological functions. We previously investigated the potential pathophysiological relationship between interleukin-18 and dyslipidemia, non-alcoholic fatty liver disease, and non-alcoholic steatohepatitis, and suggested interleukin-18 as a possible novel treatment for not only these diseases but also for cancer immunotherapy...
March 7, 2018: Journal of Translational Medicine
C Desert, E Baéza, M Aite, M Boutin, A Le Cam, J Montfort, M Houee-Bigot, Y Blum, P F Roux, C Hennequet-Antier, C Berri, S Metayer-Coustard, A Collin, S Allais, E Le Bihan, D Causeur, F Gondret, M J Duclos, S Lagarrigue
BACKGROUND: Because the cost of cereals is unstable and represents a large part of production charges for meat-type chicken, there is an urge to formulate alternative diets from more cost-effective feedstuff. We have recently shown that meat-type chicken source is prone to adapt to dietary starch substitution with fat and fiber. The aim of this study was to better understand the molecular mechanisms of this adaptation to changes in dietary energy sources through the fine characterization of transcriptomic changes occurring in three major metabolic tissues - liver, adipose tissue and muscle - as well as in circulating blood cells...
March 7, 2018: BMC Genomics
Juan Alberto Pérez-Valencia, Francisco Prosdocimi, Italo M Cesari, Igor Rodrigues da Costa, Carolina Furtado, Michelle Agostini, Franklin David Rumjanek
Metastasis of head and neck tumors is responsible for a high mortality rate. Understanding its biochemistry may allow insights into tumorigenesis. To that end we carried out RNA-Seq analyses of 5 SCC9 derived oral cancer cell lines displaying increased invasive potential. Differentially expressed genes (DEGs) were annotated based on p-values and false discovery rate (q-values). All 292 KEGG pathways related to the human genome were compared in order to pinpoint the absolute and relative contributions to the invasive process considering the 8 hallmarks of cancer plus 2 new defined categories, as well as we made with our transcriptomic data...
January 31, 2018: Scientific Reports
H B Shi, C H Zhang, Z A Xu, G G Lou, J X Liu, J Luo, J J Loor
Even though recent evidence in goat mammary epithelial cells (GMEC) suggest a role of peroxisome proliferator-activated receptor delta (PPARD) in regulating lipid homeostasis, its role is not fully understood. Our hypothesis was that PPARD regulates lipid transport processes in GMEC and, thus, plays a crucial role in regulating fat formation. The PPARD was overexpressed using an adenovirus system (Ad-PPARD) with recombinant green fluorescent protein (Ad-GFP) as the control. Results revealed that overexpression of PPARD markedly upregulated the mRNA abundance of PPARD...
January 10, 2018: Journal of Dairy Science
Natalia Martín-Martín, Amaia Zabala-Letona, Sonia Fernández-Ruiz, Leire Arreal, Laura Camacho, Mireia Castillo-Martin, Ana R Cortazar, Verónica Torrano, Ianire Astobiza, Patricia Zúñiga-García, Aitziber Ugalde-Olano, Ana Loizaga-Iriarte, Miguel Unda, Lorea Valcárcel-Jiménez, Amaia Arruabarrena-Aristorena, Marco Piva, Pilar Sánchez-Mosquera, Ana M Aransay, Antonio Gomez-Muñoz, Rosa Barrio, James D Sutherland, Arkaitz Carracedo
The nuclear receptor PPAR-β/δ (PPARD) has essential roles in fatty acid catabolism and energy homeostasis as well as cell differentiation, inflammation, and metabolism. However, its contributions to tumorigenesis are uncertain and have been disputed. Here, we provide evidence of tumor suppressive activity of PPARD in prostate cancer through a noncanonical and ligand-independent pathway. PPARD was downregulated in prostate cancer specimens. In murine prostate epithelium, PPARD gene deletion resulted in increased cellularity...
January 15, 2018: Cancer Research
Ji Ye Wang, Hong Chen, Yin Yin Wang, Xiao Qin Wang, Han Ying Chen, Mei Zhang, Yun Tang, Bo Zhang
BACKGROUND: Vitiligo is a long-term skin disease characterized by the loss of pigment in the skin. The current therapeutic approaches are limited. Although the anti-vitiligo mechanisms of Vernonia anthelmintica (L.) remain ambiguous, the herb has been broadly used in Uyghur hospitals to treat vitiligo. The overall objective of the present study aims to identify the potential lead compounds from Vernonia anthelmintica (L.) in the treatment of vitiligo via an oral route as well as the melanogenic mechanisms in the systematic approaches in silico of admetSAR and substructure-drug-target network-based inference (SDTNBI)...
November 16, 2017: BMC Systems Biology
Georgina Gyetvai, Trisha Hughes, Florence Wedmore, Cieron Roe, Lamia Heikal, Pietro Ghezzi, Manuela Mengozzi
Several studies have shown that erythropoietin (EPO) has neuroprotective or neuroreparative actions on diseases of the nervous system and that improves oligodendrocyte (OL) differentiation and myelination in vivo and in vitro. This study aims at investigating the early molecular mechanisms for the pro-myelinating action of EPO at the gene expression level. For this purpose, we used a differentiating OL precursor cell line, rat central glia-4 cells. Cells were differentiated or not, and then treated with EPO for 1 or 20 h...
2017: Frontiers in Immunology
Sibylle Sabrautzki, Gabriele Kaiser, Gerhard K H Przemeck, Felicia Gerst, Estela Lorza-Gil, Madhura Panse, Tina Sartorius, Miriam Hoene, Susan Marschall, Hans-Ulrich Häring, Martin Hrabě de Angelis, Susanne Ullrich
OBJECTIVE: The fatty acid receptor 1 (FFAR1/GPR40) mediates fatty acid-dependent augmentation of glucose-induced insulin secretion (GIIS) in pancreatic β-cells. Genetically engineered Ffar1-knockout/congenic mice univocally displayed impaired fatty acid-mediated insulin secretion, but in vivo experiments delivered controversial results regarding the function of FFAR1 in glucose homeostasis and liver steatosis. This study presents a new coisogenic mouse model carrying a point mutation in Ffar1 with functional consequence...
October 2017: Molecular Metabolism
Gary Duncan, Karl Firth, Vinoj George, Minh Duc Hoang, Andrew Staniforth, Godfrey Smith, Chris Denning
Cardiomyocytes (CMs) derived from human induced pluripotent stem cells (hiPSCs) are now a well-established modality for modeling genetic disorders of the heart. This is especially so for long QT syndrome (LQTS), which is caused by perturbation of ion channel function, and can lead to fainting, malignant arrhythmias and sudden cardiac death. LQTS2 is caused by mutations in KCNH2, a gene whose protein product contributes to IKr (also known as HERG), which is the predominant repolarizing potassium current in CMs...
December 1, 2017: Stem Cells and Development
Matthew J McLaughlin, Yang He, Janice Brunstrom-Hernandez, Liu Lin Thio, Bruce C Carleton, Colin J D Ross, Andrea Gaedigk, Andrew Lewandowski, Hongying Dai, William J Jusko, J Steven Leeder
BACKGROUND: Pharmacogenomic variability can contribute to differences in pharmacokinetics and clinical responses. Pediatric patients with cerebral palsy with genetic variations have not been studied for these potential differences. OBJECTIVE: To determine the genetic sources of variation in oral baclofen clearance and clinical responses. DESIGN: Pharmacogenomic add-on study to determine variability in oral baclofen clearance and clinical responses...
September 1, 2017: PM & R: the Journal of Injury, Function, and Rehabilitation
Afshin Hosseini, Mustafa Salman, Zheng Zhou, James K Drackley, Erminio Trevisi, Juan J Loor
BACKGROUND: The objective of the study was to evaluate the effect of overfeeding a moderate energy diet and a 2,4-thiazolidinedione (TZD) injection on blood and hepatic tissue biomarkers of lipid metabolism, oxidative stress, and inflammation as it relates to insulin sensitivity. RESULTS: Fourteen dry non-pregnant cows were fed a control (CON) diet to meet 100% of NRC requirements for 3 wk, after which half of the cows were assigned to a moderate-energy diet (OVE) and half of the cows continued on CON for 6 wk...
2017: Journal of Animal Science and Biotechnology
Dzana S Hukic, Urban Ösby, Eric Olsson, Agneta Hilding, Claes-Göran Östenson, Harvest F Gu, Ewa Ehrenborg, Gunnar Edman, Martin Schalling, Catharina Lavebratt, Louise Frisén
OBJECTIVE: We examined whether established metabolic risk genetic variants in the population confer a risk for increased waist circumference in patients with schizophrenia spectrum disorders and also an association with schizophrenia spectrum disorders irrespective of waist circumference. PATIENTS AND METHODS: We analyzed the association in (i) a case-case model in which patients with schizophrenia spectrum disorder with increased waist circumference (≥80 cm for women and ≥94 cm for men) (n=534) were compared with patients with normal waist circumference (<80 cm for women; <94 cm for men) (n=124), and in (ii) a case-control model in which schizophrenia spectrum disorder patients with increased waist circumference or irrespective of waist circumference were compared with population-derived controls (n=494) adjusted for age, sex, fasting glucose, smoking, and family history of diabetes...
December 2017: Psychiatric Genetics
Agnieszka Blitek, Magdalena Szymanska
Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear receptor family of ligand-dependent transcription factors. PPARs are critical regulators of glucose homeostasis and lipid metabolism, and affect cell proliferation and differentiation. In the current study, we examined (1) the profiles of PPARA, PPARD, and PPARG mRNA expression and DNA binding activity in porcine conceptuses collected on Days 10-11 (spherical and tubular conceptuses), 11-12 (filamentous conceptuses), 13-14, and 15-16 (elongated conceptuses) of pregnancy, (2) the presence of PPARA, PPARD, and PPARG proteins in Days 10, 12, and 15 conceptuses...
June 13, 2017: Theriogenology
Mike Hupe, Minerva Xueting Li, Susanne Kneitz, Daria Davydova, Chika Yokota, Julianna Kele-Olovsson, Belma Hot, Jan M Stenman, Manfred Gessler
The blood-brain barrier is a dynamic interface that separates the brain from the circulatory system, and it is formed by highly specialized endothelial cells. To explore the molecular mechanisms defining the unique nature of vascular development and differentiation in the brain, we generated high-resolution gene expression profiles of mouse embryonic brain endothelial cells using translating ribosome affinity purification and single-cell RNA sequencing. We compared the brain vascular translatome with the vascular translatomes of other organs and analyzed the vascular translatomes of the brain at different time points during embryonic development...
July 11, 2017: Science Signaling
L Sun, Y Shi, G Wang, X Wang, S Zeng, S E Dunn, G D Fairn, Y-J Li, D E Spaner
A deeper understanding of the mechanisms that underlie aberrant signal transduction in B-cell cancers such as chronic lymphocytic leukemia (CLL) may reveal new treatment strategies. The lipid-activated nuclear receptor peroxisome proliferator-activated receptor delta (PPARδ) accounts for a number of properties of aggressive cancers and was found to enhance Janus kinase (JAK)-mediated phosphorylation of signal transducer and activator of transcription (STAT) proteins in B lymphoma cell lines and primary CLL cells...
May 30, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
J Dou, L Zhang, X Xie, L Ye, C Yang, L Wen, C Shen, C Zhu, S Zhao, Z Zhu, B Liang, Z Wang, H Li, X Fan, S Liu, X Yin, X Zheng, L Sun, S Yang, Y Cui, F Zhou, X Zhang
BACKGROUND: Psoriasis is a complex disease influenced by both genetic and environmental factors with abnormal gene expression in lesional skin. However, no studies are available on genome-scale gene expression of psoriatic lesions in the Chinese population. In addition, systematic studies on the biological pathways, pathogenicity and interaction networks of psoriasis-related genes with abnormal expression profiles require further investigation. OBJECTIVES: To further explore the associated pathways in psoriasis by functional analysis and to identify the key genes by gene pathogenicity analysis...
November 2017: British Journal of Dermatology
Zhen Zhang, Yanyu Duan, Zhongping Wu, Hui Zhang, Jun Ren, Lusheng Huang
Peroxisome proliferator-activated receptor beta/delta (PPARD) is an important determinant of multiple biological processes. Our previous studies identified a missense mutation in the PPARD gene that significantly reduces its transcription activity, and consequently causes enlarged external ears in pigs. However, the mechanisms underlying the causality has remained largely unknown. Here, we show that PPARD retards the development of auricular cartilage by accelerating the apoptosis of cartilage stem/progenitor cells (CSPCs), the terminal differentiation of cartilage cells and the degradation of cartilage extracellular matrix in the auricle...
2017: International Journal of Biological Sciences
Katarzyna Ropka-Molik, Monika Stefaniuk-Szmukier, Kacper Żukowski, Katarzyna Piórkowska, Monika Bugno-Poniewierska
It has been found that Arabian and Thoroughbred horses differ in muscle fiber structure and thus in physiological changes occurring in muscles during exercise. The aim of the present study was to identify the global gene expression modifications that occur in skeletal muscle following a training regime to prepare for flat racing. Whole transcriptomes of muscle (gluteus medius) were compared between three time points of tissue collection: T0 (untrained horses), T1 (horses after intense gallop phase) and T2 (horses at the end of racing season), 23 samples in total...
April 28, 2017: Physiological Genomics
Wenqi Yang, Shudan Mao, Baoze Qu, Fengxiang Zhang, Zhaolong Xu
AIMS: To investigate the impact of peroxisome proliferator-activator receptor delta (PPARD) gene polymorphism and additional gene-smoking interaction on cardiovascular disease (CVD) risk based on this Chinese population. METHODS: A total of 1048 subjects (617 males, 431 females) with a mean age of 52.9 ± 14.1 years old were selected, including 520 CVD patients and 528 normal control subjects. The logistic regression model was used to examine the association between three SNPs and CVD risk, odds ratio (OR), and 95% confident interval (95%CI) were calculated...
2017: Clinical and Experimental Hypertension: CHE
P R B Silva, W J Weber, B A Crooker, R J Collier, W W Thatcher, R C Chebel
Objectives of this experiment were to evaluate the effects of recombinant bovine somatotropin (rbST) treatment of periparturient dairy cows on hepatic mRNA expression for genes related to the somatotropic axis, insulin, glucose, and lipid metabolism, inflammation, and oxidative stress. Holstein cows were enrolled in the experiment at 253 ± 3 d of gestation and assigned to 1 of 3 treatments: untreated control (n = 53), 87.5 mg of rbST (n = 56; rbST87.5), and 125 mg of rbST (n = 57; rbST125). Cows in the rbST87...
May 2017: Journal of Dairy Science
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