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https://www.readbyqxmd.com/read/29160304/il11-is-a-crucial-determinant-of-cardiovascular-fibrosis
#1
Sebastian Schafer, Sivakumar Viswanathan, Anissa A Widjaja, Wei-Wen Lim, Aida Moreno-Moral, Daniel M DeLaughter, Benjamin Ng, Giannino Patone, Kingsley Chow, Ester Khin, Jessie Tan, Sonia P Chothani, Lei Ye, Owen J L Rackham, Nicole S J Ko, Norliza E Sahib, Chee Jian Pua, Nicole T G Zhen, Chen Xie, Mao Wang, Henrike Maatz, Shiqi Lim, Kathrin Saar, Susanne Blachut, Enrico Petretto, Sabine Schmidt, Tracy Putoczki, Nuno Guimarães-Camboa, Hiroko Wakimoto, Sebastiaan van Heesch, Kristmundur Sigmundsson, See L Lim, Jia L Soon, Victor T T Chao, Yeow L Chua, Teing E Tan, Sylvia M Evans, Yee J Loh, Muhammad H Jamal, Kim K Ong, Kim C Chua, Boon-Hean Ong, Mathew J Chakaramakkil, Jonathan G Seidman, Christine E Seidman, Norbert Hubner, Kenny Y K Sin, Stuart A Cook
Fibrosis is a final common pathology in cardiovascular disease(1). In the heart, fibrosis causes mechanical and electrical dysfunction(1,2) and in the kidney, it predicts the onset of renal failure(3). Transforming growth factor β1 (TGFB1) is the principal pro-fibrotic factor(4,5) but its inhibition is associated with side effects due to its pleiotropic roles(6,7). We hypothesised that downstream effectors of TGFB1 in fibroblasts could be attractive therapeutic targets and lack upstream toxicities. Using integrated imaging-genomics analyses of primary human fibroblasts, we found that Interleukin 11 (IL11) upregulation is the dominant transcriptional response to TGFB1 exposure and required for its profibrotic effect...
November 13, 2017: Nature
https://www.readbyqxmd.com/read/29159897/identification-and-characterization-of-two-variants-of-the-hfq-srna-chaperone-in-the-fish-pathogen-piscirickettsia-salmonis
#2
S H Marshall, P Flores-Herrera, F A Henríquez, F A Gómez
Small RNA and chaperone proteins form synergistic duos that play pivotal roles in controlling gene expression in bacteria. This is the case for Hfq, a highly pleiotropic pretranslational modulator of general protein expression, which responds to harsh environmental conditions and influences fitness and virulence in a wide range of pathogenic Enterobacteria. Given this relevancy, we evaluated the presence and potential role of Hfq in the fish pathogen Piscirickettsia salmonis, a Gram-negative bacterium that threatens the sustainability of Chilean salmon production...
November 21, 2017: Journal of Fish Diseases
https://www.readbyqxmd.com/read/29158815/tethering-interleukin-22-to-apolipoprotein-a-i-ameliorates-mice-from-acetaminophen-induced-liver-injury
#3
Wei Chen, Xuyao Zhang, Jiajun Fan, Wenjing Zai, Jingyun Luan, Yubin Li, Shaofei Wang, Qicheng Chen, Yichen Wang, Yanxu Liang, Dianwen Ju
Increasing evidence indicates that interleukin-22 (IL-22) holds tremendous potential as a protective agent in preventing liver injury, but its pleiotropic effects and pathogenic role in carcinogenesis, rheumatoid arthritis and psoriasis restrict its systemic application. Here, we first developed a nanoparticle (liposIA) as a liver-targeted agent through IL-22 tethered to apolipoprotein A-I (ApoA-I) in a gene therapy vector. LiposIA was prepared using thin film dispersion method and the complexes exhibited desirable nanoparticle size, fine polydisperse index, highly efficient transfection, and excellent serum and storage stability...
2017: Theranostics
https://www.readbyqxmd.com/read/29153940/tumor-derived-cytokines-impair-myogenesis-and-alter-the-skeletal-muscle-immune-microenvironment
#4
Kelly A Hogan, Dong Seong Cho, Paige C Arneson, Adrienne Samani, Patrick Palines, Yanan Yang, Jason D Doles
Muscle wasting is a decline in skeletal muscle mass and function that is associated with aging, obesity, and a spectrum of pathologies including cancer. Cancer-associated wasting not only reduces quality of life, but also directly impacts cancer mortality, chemotherapeutic efficacy, and surgical outcomes. There is an incomplete understanding of the role of tumor-derived factors in muscle wasting and sparse knowledge of how these factors impact in vivo muscle regeneration. Here, we identify several cytokines/chemokines that negatively impact in vitro myogenic differentiation...
November 16, 2017: Cytokine
https://www.readbyqxmd.com/read/29153377/iatrogenic-iron-overload-and-its-potential-consequences-in-patients-on-hemodialysis
#5
Guy Rostoker, Nosratola D Vaziri
Iron overload was considered rare in hemodialysis patients until recently, but its clinical frequency is now increasingly recognized. The liver is the main site of iron storage and the liver iron concentration (LIC) is closely correlated with total iron stores in patients with secondary hemosiderosis and genetic hemochromatosis. Magnetic resonance imaging (MRI) is now the gold standard method for estimating and monitoring LIC. Studies of LIC in hemodialysis patients by magnetic susceptometry thirteen years ago and recently by quantitative MRI have demonstrated a relation between the risk of iron overload and the use of intravenous (IV) iron products prescribed at doses determined by the iron biomarker cutoffs contained in current anemia management guidelines...
November 16, 2017: La Presse Médicale
https://www.readbyqxmd.com/read/29151225/association-between-different-dietary-polyphenol-subclasses-and-the-improvement-in-cardiometabolic-risk-factors-evidence-from-a-randomized-controlled-clinical-trial
#6
Claudia Vetrani, Marilena Vitale, Lutgarda Bozzetto, Giuseppe Della Pepa, Sara Cocozza, Giuseppina Costabile, Anna Mangione, Paola Cipriano, Giovanni Annuzzi, Angela A Rivellese
AIMS: Due to their different chemical structures and metabolism, polyphenol subclasses may have specific impact on cardiometabolic risk factors. Our aim was to evaluate whether the intake of different polyphenol subclasses is associated with clinical outcomes beneficially improved by polyphenols in a nutritional trial performed by our group (postprandial lipid response, glucose homeostasis, early insulin secretion and oxidative stress). METHODS: The present study is a secondary analysis of a nutritional intervention study with a diet naturally rich in polyphenols...
November 18, 2017: Acta Diabetologica
https://www.readbyqxmd.com/read/29151067/the-x-a-like-cell-revisited-spotlight-on-the-peripheral-effects-of-nucb2-nesfatin-1-and-ghrelin
#7
E Weibert, A Stengel
The gastric X/A-like cell was long thought to be restricted to the production of acyl ghrelin. However, the subsequent years witnessed the discovery of other peptide products derived from this cell, namely desacyl ghrelin, obestatin and nesfatin-1. While the role of obestatin remains highly questionable and is very critically discussed in the literature, besides acyl ghrelin also desacyl ghrelin and nesfatin-1 have been implicated in the regulation of food intake. As observed for several other peptide hormones before, ghrelin and nesfatin-1 are not restricted to one function but rather exert pleiotropic actions including effects on gastrointestinal motility, thermogenesis, lipid and glucose homeostasis, stress mediation, cardiovascular as well as reproductive functions...
August 2017: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/29150697/a-novel-allele-of-tagw2-a1-is-located-in-a-finely-mapped-qtl-that-increases-grain-weight-but-decreases-grain-number-in-wheat-triticum-aestivum-l
#8
Huijie Zhai, Zhiyu Feng, Xiaofen Du, Yane Song, Xinye Liu, Zhongqi Qi, Long Song, Jiang Li, Linghong Li, Huiru Peng, Zhaorong Hu, Yingyin Yao, Mingming Xin, Shihe Xiao, Qixin Sun, Zhongfu Ni
A novel TaGW2-A1 allele was identified from a stable, robust QTL region, which is pleiotropic for thousand grain weight, grain number per spike, and grain morphometric parameters in wheat. Thousand grain weight (TGW) and grain number per spike (GNS) are two crucial determinants of wheat spike yield, and genetic dissection of their relationships can help to fine-tune these two components and maximize grain yield. By evaluating 191 recombinant inbred lines in 11 field trials, we identified five genomic regions on chromosomes 1B, 3A, 3B, 5B, or 7A that solely influenced either TGW or GNS, and a further region on chromosome 6A that concurrently affected TGW and GNS...
November 17, 2017: TAG. Theoretical and Applied Genetics. Theoretische und Angewandte Genetik
https://www.readbyqxmd.com/read/29150481/identification-of-pleiotropic-cancer-susceptibility-variants-from-genome-wide-association-studies-reveals-functional-characteristics
#9
Yi-Hsuan Wu, Rebecca E Graff, Michael N Passarelli, Joshua D Hoffman, Elad Ziv, Thomas J Hoffmann, John S Witte
BACKGROUND: There exists compelling evidence that some genetic variants are associated with the risk of multiple cancer sites (i.e., pleiotropy). However, the biological mechanisms through which the pleiotropic variants operate are unclear. METHODS: We obtained all cancer risk associations from the National Human Genome Research Institute-European Bioinformatics Institute GWAS Catalog, and correlated cancer risk variants were clustered into groups. Pleiotropic variant groups and genes were functionally annotated...
November 17, 2017: Cancer Epidemiology, Biomarkers & Prevention
https://www.readbyqxmd.com/read/29149821/statins-therapy-for-connective-tissue-diseases-new-therapeutic-opportunities
#10
Przemyslaw J Kotyla, Eugene J Kucharz
Background and Objective Statins, 3-hydroxyl-3-methyl-glutharyl Coenzyme A reductase inhibitors showed their therapeutic potential in the treatment of atherosclerosis-related diseases. Recently, the properties of statins, separate from their lipid lowering activity have attracted much attention. These properties that cover a wide area of physiopathological activities including cell maturation, immune response regulation, tissue fibrosis, endothelial activity and are called pleiotropic activity. Many in vitro studies demonstrated significant, statins-dependent regulation of immune system reactivity, reduction of pro-inflammatory and pro-fibrotic cytokines as well as suppression of endothelial activity and damage...
November 15, 2017: Endocrine, Metabolic & Immune Disorders Drug Targets
https://www.readbyqxmd.com/read/29149405/current-understanding-of-the-tctp-interactome
#11
Siting Li, Feng Ge
Evolutionarily conserved and pleiotropic, the translationally controlled tumor protein (TCTP) is a housekeeping protein present in eukaryotic organisms. It plays an important role in regulating many fundamental processes, such as cell proliferation, cell death, immune responses, and apoptosis. As a result of the pioneer work by Adam Telerman and Robert Amson, the critical role of TCTP in tumor reversion was revealed. Moreover, TCTP has emerged as a regulator of cell fate determination and a promising therapeutic target for cancers...
2017: Results and Problems in Cell Differentiation
https://www.readbyqxmd.com/read/29149079/sphingosine-1-phosphate-s1p-signaling-in-glioblastoma-multiforme-a-systematic-review
#12
REVIEW
Shailaja Mahajan-Thakur, Sandra Bien-Möller, Sascha Marx, Henry Schroeder, Bernhard H Rauch
The multifunctional sphingosine-1-phosphate (S1P) is a lipid signaling molecule and central regulator in the development of several cancer types. In recent years, intriguing information has become available regarding the role of S1P in the progression of Glioblastoma multiforme (GBM), the most aggressive and common brain tumor in adults. S1P modulates numerous cellular processes in GBM, such as oncogenesis, proliferation and survival, invasion, migration, metastasis and stem cell behavior. These processes are regulated via a family of five G-protein-coupled S1P receptors (S1PR1-5) and may involve mainly unknown intracellular targets...
November 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29147820/cue-signal-response-analysis-in-3d-chondrocyte-scaffolds-with-anabolic-stimuli
#13
Michael Neidlin, Antonion Korcari, Giorgos Macheras, Leonidas G Alexopoulos
Articular cartilage is an avascular connective tissue responsible for bearing loads. Cell signaling plays a central role in cartilage homeostasis and tissue engineering by directing chondrocytes to synthesize/degrade the extracellular matrix or promote inflammatory responses. The aim of this paper was to investigate anabolic, catabolic and inflammatory pathways of well-known and underreported anabolic stimuli in 3D chondrocyte cultures and connect them to diverse cartilage responses including matrix regeneration and cell communication...
November 16, 2017: Annals of Biomedical Engineering
https://www.readbyqxmd.com/read/29145611/identification-of-novel-potentially-pleiotropic-variants-associated-with-osteoporosis-and-obesity-using-cfdr-method
#14
Yuan Hu, Li-Jun Tan, Xiang-Ding Chen, Zhen Liu, Shi-Shi Min, Qin Zeng, Hui Shen, Hong-Wen Deng
Context: Genome-wide association studies (GWASs) have been successful in identifying loci associated with osteoporosis and obesity. However, the findings just explain a small fraction of the total genetic variance. Objective: The aim of this study was to identify novel pleiotropic genes important in osteoporosis and obesity. Design and Setting: A pleiotropic conditional false discovery rate (cFDR) method was applied to three independent GWAS summary statistics of femoral neck bone mineral density (FN BMD), body mass index (BMI) and waist-hip ratio (WHR)...
November 14, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29145610/transition-to-an-aquatic-habitat-permitted-the-repeated-loss-of-the-pleiotropic-klk8-gene-in-mammals
#15
Nikolai Hecker, Virag Sharma, Michael Hiller
KLK8 (also called neuropsin) is a serine protease that plays distinct roles in the skin and hippocampus. In the skin, KLK8 influences keratinocyte proliferation and desquamation, and activates antimicrobial peptides in sweat. In the hippocampus, KLK8 affects memory acquisition. Here, we examined the evolution of KLK8 in mammals and discovered that, out of 70 placental mammals, KLK8 is exclusively lost in three independent fully-aquatic lineages, comprising dolphin, killer whale, minke whale and manatee. In addition, while the sperm whale has an intact KLK8 reading frame, the gene evolves neutrally in this species...
November 14, 2017: Genome Biology and Evolution
https://www.readbyqxmd.com/read/29145473/suppression-and-resolution-of-autoimmune-arthritis-by-rhesus-%C3%AE-defensin-1-an-immunomodulatory-macrocyclic-peptide
#16
Justin B Schaal, Dat Q Tran, Akshay Subramanian, Reshma Patel, Teresina Laragione, Kevin D Roberts, Katie Trinh, Prasad Tongaonkar, Patti A Tran, Dmitriy Minond, Gregg B Fields, Paul Beringer, André J Ouellette, Percio S Gulko, Michael E Selsted
θ-defensins constitute a family of macrocyclic peptides expressed exclusively in Old World monkeys. The peptides are pleiotropic effectors of innate immunity, possessing broad spectrum antimicrobial activities and immunoregulatory properties. Here we report that rhesus θ-defensin 1 (RTD-1) is highly effective in arresting and reversing joint disease in a rodent model of rheumatoid arthritis (RA). Parenteral RTD-1 treatment of DA/OlaHsd rats with established pristane-induced arthritis (PIA) rapidly suppressed joint disease progression, restored limb mobility, and preserved normal joint architecture...
2017: PloS One
https://www.readbyqxmd.com/read/29143341/a-toxicogenomics-approach-to-screen-chlorinated-flame-retardants-tris-2-chloroethyl-phosphate-and-tris-2-chloroisopropyl-phosphate-for-potential-health-effects
#17
Boris V Krivoshiev, Gerrit T S Beemster, Katrien Sprangers, Ronny Blust, Steven J Husson
Tris(2-chloroethyl) phosphate (TCEP) is a pervasive flame retardant that has been identified as a chemical of concern given its health effects and therefore its use has since been tightly regulated. Tris(2-chloroisopropyl) phosphate (TCIPP), an analogue of TCEP, is believed to be its replacement. However, compared to TCEP, little is known of the toxicological impacts of TCIPP. We used RNA sequencing as unbiased and sensitive tool to identify and compare effects on a transcriptome level of TCEP and TCIPP in the human hepatocellular carcinoma cell line, HepG2...
November 16, 2017: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/29143311/interleukin-12-and-its-procoagulant-effect-on-erythrocytes-platelets-and-fibrin-ogen-the-lesser-known-side-of-inflammation
#18
Martin J Page, Janette Bester, Etheresia Pretorius
Inflammation, with its associated inflammatory molecules, is integral to most chronic diseases, including the various cardiovascular diseases. Interleukin 12 (IL12) is one of the inflammatory cytokines that is upregulated during inflammation; however, we know very little about its exact effect on red blood cells (RBCs), platelets and fibrin(ogen). IL12 is an important pleiotropic cytokine in early inflammatory responses and has potent immunomodulatory, antitumour and anti-infection activity. Here we investigate how low levels of circulating IL12, comparable to levels found during chronic inflammation, affect coagulation parameters, platelets and RBCs...
November 16, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/29142377/serum-vitamin-d-status-and-outcome-in-critically-ill-children
#19
Nazik Aşılıoğlu, Halit Çiǧdem, Muhammed Sükrü Paksu
Background: Vitamin D is a pleiotropic hormone essential for optimal health. Critical illness in children is a major cause of significant health-care utilization and mortality around the world. The association of Vitamin D deficiency (VDD) in critically ill adults has been well-studied, in comparison, the importance of Vitamin D in pediatric critical illness has been much less studied. Aim and Objectives: This study aimed to assess Vitamin D status and its determinants in patients admitted to a pediatric intensive care unit (PICU) in North of Turkey...
October 2017: Indian Journal of Critical Care Medicine
https://www.readbyqxmd.com/read/29142375/the-effects-of-atorvastatin-on-inflammatory-responses-and-mortality-in-septic-shock-a-single-center-randomized-controlled-trial
#20
Ratender Kumar Singh, Vikas Agarwal, Arvind Kumar Baronia, Sudeep Kumar, Banani Poddar, Afzal Azim
Aim of the Study: Pleiotropic effect of statins can modulate inflammation in septic shock. We tested the hypothesis whether statins can reduce mortality in septic shock. Patients and Methods: We conducted a randomized double-blinded trial with treatment (40 mg dose of atorvastatin for 7 days) and control (placebo) arm in adult septic shock patients admitted to the Intensive Care Unit. Primary (28-day mortality) and secondary (vasopressor-, ventilation-, and renal replacement therapy-free days) outcomes, with lipid profile and adverse effects, were documented...
October 2017: Indian Journal of Critical Care Medicine
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