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https://www.readbyqxmd.com/read/28343015/systemic-delivery-of-the-tumor-necrosis-factor-gene-to-tumors-by-a-novel-dual-dna-nanocomplex-in-a-nanoparticle-system
#1
Vasundhara Shukla, Manu Dalela, Manika Vij, Munia Ganguli, Ralph Weichselbaum, Surender Kharbanda, Donald Kufe, Harpal Singh
Many cancers fail to respond to immunotherapy as a result of immune suppression by the tumor microenvironment. The exogenous expression of immune cytokines to reprogram the tumor microenvironment represents an approach to circumvent this suppression. The present studies describe the development of a novel dual nanoparticle (DNP) system for driving DNA expression vectors encoding inflammatory cytokines in tumor cells. The DNP system consists of a DNA expression vector-cationic nanocomplex (NC) surrounded by a diblock polymeric NP...
March 22, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/28320879/metabolism-shapes-the-cell
#2
Anthony M Sperber, Jennifer K Herman
More than five decades of work support the idea that cell envelope synthesis, including the inward growth of cell division, is tightly coordinated with DNA replication and protein synthesis through central metabolism. Remarkably, no unifying model exists to account for how these fundamentally disparate processes are functionally coupled. Recent studies demonstrate that proteins involved in carbohydrate and nitrogen metabolism can moonlight as direct regulators of cell division, coordinate cell division and DNA replication, and even suppress defects in DNA replication...
March 20, 2017: Journal of Bacteriology
https://www.readbyqxmd.com/read/28294872/-pleotropic-effects-of-atorvastatin-in-patients-with-chronic-ischemic-heart-disease
#3
V P Mikhin, Yu A Zhilyaeva, N I Gromnaky
Examined 52 patients with a diagnosis Ischemic heart disease: stable angina II-III FC CHF I-IIA stage, in combination with hypercholesterolemia aged 53-65 years (58,2+/-6,5), receiving together with traditional antianginal therapy generic atorvastatin Torvakard in the dose of 10 mg/day (20 people) with the level of total cholesterol from 5.0 to 6.50 mmol/l, patients with cholesterol levels from is 6.51 to 8.0 mmol/l was taking Torvakard 20 mg/day (32 person). As a result of 3 months therapy with low doses of Torvakarda decreased level of CRP, endothelin-1, IMT, improving the parameters of endothelium-dependent vasodilation, which shows the positive impact of the drug on morphological and functional parameters of the vascular wall...
May 2016: Kardiologiia
https://www.readbyqxmd.com/read/28256636/elevated-fibroblast-growth-factor-21-fgf21-in-obese-insulin-resistant-states-is-normalised-by-the-synthetic-retinoid-fenretinide-in-mice
#4
Nicola Morrice, George D Mcilroy, Seshu R Tammireddy, Jennifer Reekie, Kirsty D Shearer, Mary K Doherty, Mirela Delibegović, Phillip D Whitfield, Nimesh Mody
Fibroblast growth factor 21 (FGF21) has emerged as an important beneficial regulator of glucose and lipid homeostasis but its levels are also abnormally increased in insulin-resistant states in rodents and humans. The synthetic retinoid Fenretinide inhibits obesity and improves glucose homeostasis in mice and has pleotropic effects on cellular pathways. To identify Fenretinide target genes, we performed unbiased RNA-seq analysis in liver from mice fed high-fat diet ± Fenretinide. Strikingly, Fgf21 was the most downregulated hepatic gene...
March 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28239611/pleotropic-acute-and-chronic-effects-of-leptin-to-reverse-type-1-diabetes
#5
Rachel J Perry
Recent studies have demonstrated that leptin can prolong life chronically in rats with poorly-controlled type 1 diabetes (T1D). Multiple explanations have been proposed to explain leptin's chronic antihyperglycemic effect, including suppression of glucagon release and/or signaling, reductions in hyperphagia and ectopic lipid content, and improvements in insulin sensitivity; it is leptin's ability to reduce plasma glucose relies on all of these effects. In addition, leptin reverses hyperglycemia and diabetic ketoacidosis (DKA) acutely, within 6 hours of leptin infusion, by suppressing hypothalamic-pituitary-adrenal (HPA) axis activity in insulinopenic rats...
January 2017: Postdoc Journal: a Journal of Postdoctoral Research and Postdoctoral Affairs
https://www.readbyqxmd.com/read/28166722/integration-of-vdr-genome-wide-binding-and-gwas-genetic-variation-data-reveals-co-occurrence-of-vdr-and-nf-%C3%AE%C2%BAb-binding-that-is-linked-to-immune-phenotypes
#6
Prashant K Singh, Patrick R van den Berg, Mark D Long, Angie Vreugdenhil, Laurie Grieshober, Heather M Ochs-Balcom, Jianmin Wang, Sylvie Delcambre, Sami Heikkinen, Carsten Carlberg, Moray J Campbell, Lara E Sucheston-Campbell
BACKGROUND: The nuclear hormone receptor superfamily acts as a genomic sensor of diverse signals. Their actions are often intertwined with other transcription factors. Nuclear hormone receptors are targets for many therapeutic drugs, and include the vitamin D receptor (VDR). VDR signaling is pleotropic, being implicated in calcaemic function, antibacterial actions, growth control, immunomodulation and anti-cancer actions. Specifically, we hypothesized that the biologically significant relationships between the VDR transcriptome and phenotype-associated biology could be discovered by integrating the known VDR transcription factor binding sites and all published trait- and disease-associated SNPs...
February 6, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28164169/adeno-associated-virus-serotype-9-driven-expression-of-bag3-improves-left-ventricular-function-in-murine-hearts-with-left-ventricular-dysfunction-secondary-to-a-myocardial-infarction
#7
Tijana Knezevic, Valerie D Myers, Feifei Su, JuFang Wang, Jianliang Song, Xue-Qian Zhang, Erhe Gao, Guofeng Gao, Madesh Muniswamy, Manish K Gupta, Jennifer Gordon, Kristen N Weiner, Joseph Rabinowitz, Frederick V Ramsey, Douglas G Tilley, Kamel Khalili, Joseph Y Cheung, Arthur M Feldman
OBJECTIVES: The present study was undertaken to test the hypothesis that gene delivery of BCL2-Associated Athanogene 3 (BAG3) to the heart of mice with left ventricular dysfunction secondary to a myocardial infarction could enhance cardiac performance. BACKGROUND: BAG3 is a 575 amino acid protein that has pleotropic functions in the cell including pro-autophagy and anti-apoptosis. Mutations in BAG3 have been associated with both skeletal muscle dysfunction and familial dilated cardiomyopathy and BAG3 levels are diminished in non-familial heart failure...
December 2016: JACC. Basic to Translational Science
https://www.readbyqxmd.com/read/28163307/role-of-nad-and-mitochondrial-sirtuins-in-cardiac-and-renal-diseases
#8
REVIEW
Kathleen A Hershberger, Angelical S Martin, Matthew D Hirschey
The coenzyme nicotinamide adenine dinucleotide (NAD(+)) has key roles in the regulation of redox status and energy metabolism. NAD(+) depletion is emerging as a major contributor to the pathogenesis of cardiac and renal diseases and NAD(+) repletion strategies have shown therapeutic potential as a means to restore healthy metabolism and physiological function. The pleotropic roles of NAD(+) enable several possible avenues by which repletion of this coenzyme could have therapeutic efficacy. In particular, NAD(+) functions as a co-substrate in deacylation reactions carried out by the sirtuin family of enzymes...
February 6, 2017: Nature Reviews. Nephrology
https://www.readbyqxmd.com/read/28144995/axonal-neuropathies-due-to-mutations-in-small-heat-shock-proteins-clinical-genetic-and-functional-insights-into-novel-mutations
#9
Andoni Echaniz-Laguna, Thomas Geuens, Philippe Petiot, Yann Péréon, Elias Adriaenssens, Mansour Haidar, Simona Capponi, Thierry Maisonobe, Emmanuel Fournier, Odile Dubourg, Bertrand Degos, François Salachas, Timothée Lenglet, Bruno Eymard, Emilien Delmont, Jean Pouget, Raul Juntas Morales, Cyril Goizet, Philippe Latour, Vincent Timmerman, Tanya Stojkovic
In this study, we describe the phenotypic spectrum of distal hereditary motor neuropathy caused by mutations in the small heat shock proteins HSPB1 and HSPB8 and investigate the functional consequences of newly discovered variants. Among 510 unrelated patients with distal motor neuropathy, we identified mutations in HSPB1 (28 index patients/510; 5.5%) and HSPB8 (four index patients/510; 0.8%) genes. Patients have slowly progressive distal (100%) and proximal (13%) weakness in lower limbs (100%), mild lower limbs sensory involvement (31%), foot deformities (73%), progressive distal upper limb weakness (29%), mildly raised serum creatine kinase levels (100%), and central nervous system involvement (9%)...
February 1, 2017: Human Mutation
https://www.readbyqxmd.com/read/28112679/mechanism-for-leptin-s-acute-insulin-independent-effect-to-reverse-diabetic-ketoacidosis
#10
Rachel J Perry, Liang Peng, Abudukadier Abulizi, Lynn Kennedy, Gary W Cline, Gerald I Shulman
The mechanism by which leptin reverses diabetic ketoacidosis (DKA) is unknown. We examined the acute insulin-independent effects of leptin replacement therapy in a streptozotocin-induced rat model of DKA. Leptin infusion reduced rates of lipolysis, hepatic glucose production (HGP), and hepatic ketogenesis by 50% within 6 hours and were independent of any changes in plasma glucagon concentrations; these effects were abrogated by coinfusion of corticosterone. Treating leptin- and corticosterone-infused rats with an adipose triglyceride lipase inhibitor blocked corticosterone-induced increases in plasma glucose concentrations and rates of HGP and ketogenesis...
February 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28052118/tgf-%C3%AE-3-inhibits-antibody-production-by-human-b-cells
#11
Yumi Tsuchida, Shuji Sumitomo, Kazuyoshi Ishigaki, Akari Suzuki, Yuta Kochi, Haruka Tsuchiya, Mineto Ota, Toshihiko Komai, Mariko Inoue, Kaoru Morita, Tomohisa Okamura, Kazuhiko Yamamoto, Keishi Fujio
TGF-β is a pleotropic cytokine involved in various biological processes. Of the three isoforms of TGF-β, TGF-β1 has long been recognized as an important inhibitory cytokine in the immune system and has been reported to inhibit B cell function in both mice and humans. Recently, it has been suggested that TGF-β3 may play an important role in the regulation of immune system in mice. Murine CD4+CD25-LAG3+ regulatory T cells suppress B cell function through the production of TGF-β3, and it has been reported that TGF-β3 is therapeutic in a mouse model of systemic lupus erythematosus...
2017: PloS One
https://www.readbyqxmd.com/read/28004134/genetic-analysis-and-mapping-of-adult-plant-resistance-loci-to-leaf-rust-in-durum-wheat-cultivar-bairds
#12
Caixia Lan, Bhoja R Basnet, Ravi P Singh, Julio Huerta-Espino, Sybil A Herrera-Foessel, Yong Ren, Mandeep S Randhawa
New leaf rust adult plant resistance (APR) QTL QLr.cim - 6BL was mapped and confirmed the known pleotropic APR gene Lr46 effect on leaf rust in durum wheat line Bairds. CIMMYT-derived durum wheat line Bairds displays an adequate level of adult plant resistance (APR) to leaf rust in Mexican field environments. A recombinant inbred line (RIL) population developed from a cross of Bairds with susceptible parent Atred#1 was phenotyped for leaf rust response at Ciudad Obregon, Mexico, during 2013, 2014, 2015 and 2016 under artificially created epidemics of Puccinia triticina (Pt) race BBG/BP...
March 2017: TAG. Theoretical and Applied Genetics. Theoretische und Angewandte Genetik
https://www.readbyqxmd.com/read/27943080/kostmann-s-disease-and-hcls1-associated-protein-x-1-hax1
#13
REVIEW
Christoph Klein
Severe congenital neutropenia (SCN), originally described by the Swedish pediatrician Rolf Kostmann, constitutes a heterogeneous disorder associated with a dramatic decrease of peripheral neutrophil granulocytes. Patients suffer from life-threatening bacterial infections unless treated by recombinant human granulocyte colony stimulating factor (G-CSF) or allogeneic hematopoietic stem cells. This review is focused on the SCN variant caused by mutations in HCLS1 Associated Protein X-1 (HAX1) (SCN3, "Kostmann Disease")...
February 2017: Journal of Clinical Immunology
https://www.readbyqxmd.com/read/27908965/inf-%C3%AE-encoding-plasmid-administration-triggers-bone-loss-and-disrupts-bone-marrow-microenvironment
#14
Dimitrios Agas, Guilherme Gusmão Silva, Fulvio Laus, Andrea Marchegiani, Melania Capitani, Cecilia Vullo, Giuseppe Catone, Giovanna Lacava, Antonio Concetti, Luigi Marchetti, Maria Giovanna Sabbieti
IFN-γ is a pleotropic cytokine produced in the bone microenvironment. Although IFN-γ is known to play a critical role on bone remodeling, its function is not fully elucidated. Consistently, outcomes on the effects of IFN-γ recombinant protein on bone loss are contradictory among reports. In our work we explored, for the first time, the role of IFN-γ encoding plasmid (pIFN-γ) in a mouse model of osteopenia induced by ovariectomy and in the sham-operated counterpart to estimate its effects in skeletal homeostasis...
February 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/27879405/does-citrulline-sit-at-the-nexus-of-metformin-s-pleotropic-effects-on-metabolism-and-mediate-its-salutatory-effects-in-individuals-with-type-2-diabetes
#15
Brian A Irving, Guillaume Spielmann
No abstract text is available yet for this article.
December 2016: Diabetes
https://www.readbyqxmd.com/read/27836669/genetic-deletion-of-galectin-3-enhances-neuroinflammation-affects-microglial-activation-and-contributes-to-sub-chronic-injury-in-experimental-neonatal-focal-stroke
#16
Sophorn Chip, David Fernández-López, Fan Li, Joel Faustino, Nikita Derugin, Zinaida S Vexler
The pathophysiology of neonatal stroke and adult stroke are distinct in many aspects, including the inflammatory response. We previously showed endogenously protective functions of microglial cells in acute neonatal stroke. We asked if galectin-3 (Gal3), a pleotropic molecule that mediates interactions between microglia/macrophages and the extracellular matrix (ECM), plays a role in early injury after transient middle cerebral occlusion (tMCAO) in postnatal day 9-10 mice. Compared to wild type (WT) pups, in Gal3 knockout pups injury was worse and cytokine/chemokine production altered, including further increase of MIP1α and MIP1β levels and reduced IL6 levels 72h after tMCAO...
February 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/27785114/lipoprotein-apheresis-in-the-management-of-severe-hypercholesterolemia-and-of-elevation-of-lipoprotein-a-current-perspectives-and-patient-selection
#17
REVIEW
Ulrich Julius
This review reports the current situation with respect to therapeutic options (lifestyle and drugs) reducing the concentrations of atherogenic low-density lipoprotein cholesterol (LDL-C) and lipoprotein(a) (Lp[a]). Three lipoprotein apheresis (LA) principles have been realized: precipitation, filtration, and adsorption. Available LA methods are herein described in detail - major components, pumps, extracorporeal volume, treated volume, and anticoagulation. General features of all LA methods as well as pleotropic effects are elaborated...
2016: Medical Devices: Evidence and Research
https://www.readbyqxmd.com/read/27720306/epigenetic-regulation-of-pro-inflammatory-cytokine-secretion-by-sphingosine-1-phosphate-s1p-in-acute-lung-injury-role-of-s1p-lyase
#18
REVIEW
David L Ebenezer, Panfeng Fu, Vidyani Suryadevara, Yutong Zhao, Viswanathan Natarajan
Cellular level of sphingosine-1-phosphate (S1P), the simplest bioactive sphingolipid, is tightly regulated by its synthesis catalyzed by sphingosine kinases (SphKs) 1 & 2 and degradation mediated by S1P phosphatases, lipid phosphate phosphatases, and S1P lyase. The pleotropic actions of S1P are attributed to its unique inside-out (extracellular) signaling via G-protein-coupled S1P1-5 receptors, and intracellular receptor independent signaling. Additionally, S1P generated in the nucleus by nuclear SphK2 modulates HDAC1/2 activity, regulates histone acetylation, and transcription of pro-inflammatory genes...
January 2017: Advances in Biological Regulation
https://www.readbyqxmd.com/read/27684953/quantitative-proteomic-profiling-the-molecular-signatures-of-annexin-a5-in-lung-squamous-carcinoma-cells
#19
Bing Sun, Yuxin Bai, Liyuan Zhang, Linlin Gong, Xiaoyu Qi, Huizhen Li, Faming Wang, Xinming Chi, Yulin Jiang, Shujuan Shao
Lung cancer remains the leading cancer killer around the world. It's crucial to identify newer mechanism-based targets to effectively manage lung cancer. Annexin A5 (ANXA5) is a protein kinase C inhibitory protein and calcium dependent phospholipid-binding protein, which may act as an endogenous regulator of various pathophysiological processes. However, its molecular mechanism in lung cancer remains poorly understood. This study was designed to determine the mechanism of ANXA5 in lung cancer with a hope to obtain useful information to provide a new therapeutic target...
2016: PloS One
https://www.readbyqxmd.com/read/27633970/epoxyeicosatrienoic-acid-as-therapy-for-diabetic-and-ischemic-cardiomyopathy
#20
Mikhail Romashko, Joseph Schragenheim, Nader G Abraham, John A McClung
Cardiovascular disease remains the leading cause of death worldwide. Among many potential targets for pharmacological intervention, a promising strategy involves epoxyeicosatrienoic acid (EET) and soluble epoxide hydroxylase (sEH) inhibition. sEH is the enzyme that converts EET to its less potent metabolite; therefore, EET is upregulated by its inhibitor. EET has pleotropic effects that collectively reduce inflammation, while increasing vasodilation and insulin sensitivity. Recent reports indicate that EET agonists and sEH inhibitors are capable of not only reversing endothelial dysfunction and hypertension, but also of reversing cardiac remodeling, which is a hallmark of cardiomyopathy and the metabolic syndrome...
September 12, 2016: Trends in Pharmacological Sciences
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