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https://www.readbyqxmd.com/read/27910098/gata-3-specific-dnazyme-a-novel-approach-for-stratified-asthma-therapy
#1
REVIEW
Holger Garn, Harald Renz
It is now well established that type-2 immune mechanisms drive the inflammation in about 50% of asthma patients. The major cellular and molecular players regulating this important network have been identified. In terms of therapeutic intervention, cytokine and cytokine-receptor pathways have been given major attention, since these molecules are relatively easily accessible for a blockade through monoclonal antibodies, and a number of positive clinical results support this concept. However, targeting events controlling the type-2 immunity network upstream of selective cytokine pathways would be equally attractive...
December 2, 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/27909943/simulating-different-dosing-scenarios-for-a-child-appropriate-valproate-er-formulation-in-a-new-pediatric-two-stage-dissolution-model
#2
Frank Karkossa, Antonia Krueger, Jana Urbaniak, Sandra Klein
Predictive in vitro test methods addressing the parameters relevant to drug release in the pediatric gastrointestinal tract could be an appropriate means for reducing the number of in vivo studies in children. However, dissolution models addressing the particular features of pediatric gastrointestinal physiology and typical pediatric dosing scenarios have not yet been described. The objective of the present study was to combine the knowledge on common vehicle types and properties and current information on pediatric gastrointestinal physiology to design a dissolution model that enables a biorelevant simulation of the gastrointestinal conditions in young children...
December 1, 2016: AAPS PharmSciTech
https://www.readbyqxmd.com/read/27908414/licl-regulates-mitochondrial-biogenesis-during-megakaryocyte-development
#3
Ram Babu Undi, Usha Gutti, Ravi Kumar Gutti
JAK-STAT, PI3K-AKT and MAPK signaling pathways are involved in platelet production process. Although wnt signaling has been reported in the biogenesis of platelets, but its role in megakaryocyte development is not well studied. We used an inducible canonical wnt signaling system that utilizes LiCl (GSK-3β inhibitor). LiCl could activate wnt signaling pathway along with maturation of megakaryocytes. Mitochondrial staining showed an increase in mitochondrial mass upon induction with LiCl. Also, mitochondrial markers PGC-1α and TFAM were up regulated with increase in mitochondrial DNA content...
January 2017: Journal of Trace Elements in Medicine and Biology
https://www.readbyqxmd.com/read/27907166/vaccinia-virus-protein-c6-inhibits-type-i-ifn-signalling-in-the-nucleus-and-binds-to-the-transactivation-domain-of-stat2
#4
Jennifer H Stuart, Rebecca P Sumner, Yongxu Lu, Joseph S Snowden, Geoffrey L Smith
The type I interferon (IFN) response is a crucial innate immune signalling pathway required for defense against viral infection. Accordingly, the great majority of mammalian viruses possess means to inhibit this important host immune response. Here we show that vaccinia virus (VACV) strain Western Reserve protein C6, is a dual function protein that inhibits the cellular response to type I IFNs in addition to its published function as an inhibitor of IRF-3 activation, thereby restricting type I IFN production from infected cells...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27906090/muscle-specific-deletion-of-socs3-increases-the-early-inflammatory-response-but-does-not-affect-regeneration-after-myotoxic-injury
#5
Kristy Swiderski, Savant S Thakur, Timur Naim, Jennifer Trieu, Annabel Chee, David I Stapleton, René Koopman, Gordon S Lynch
BACKGROUND: Muscles of old animals are injured more easily and regenerate poorly, attributed in part to increased levels of circulating pro-inflammatory cytokines. The Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling cascade is a key mediator of inflammatory cytokine action, and signaling via this pathway is increased in muscles with aging. As a negative regulator of JAK/STAT signaling, a key mediator of myogenic proliferation and differentiation, altered expression of suppressor of cytokine signaling (SOCS3) is likely to have important consequences for muscle regeneration...
October 24, 2016: Skeletal Muscle
https://www.readbyqxmd.com/read/27905454/stat-checking-software-stirs-up-psychology
#6
Monya Baker
No abstract text is available yet for this article.
November 25, 2016: Nature
https://www.readbyqxmd.com/read/27903278/an-overview-on-the-role-of-dietary-phenolics-for-the-treatment-of-cancers
#7
REVIEW
Preethi G Anantharaju, Prathima C Gowda, Manjunatha G Vimalambike, SubbaRao V Madhunapantula
Plant derived phenolic compounds have been shown to inhibit the initiation and progression of cancers by modulating genes regulating key processes such as: (a) oncogenic transformation of normal cells; (b) growth and development of tumors; and (c) angiogenesis and metastasis. Recent studies focusing on identifying the molecular basis of plant phenolics-induced cancer cell death have demonstrated down-regulation of: (a) oncogenic survival kinases such as PI3K and Akt; (b) cell proliferation regulators that include Erk1/2, D-type Cyclins, and Cyclin Dependent Kinases (CDKs); (c) transcription factors such as NF-kβ, NRF2 and STATs; (d) histone deacetylases HDAC1 and HDAC2; and (e) angiogenic factors VEGF, FGFR1 and MIC-1...
December 1, 2016: Nutrition Journal
https://www.readbyqxmd.com/read/27901106/the-role-of-pim1-pim2-kinases-in-tumors-of-the-male-reproductive-system
#8
Manuel Pedro Jiménez-García, Antonio Lucena-Cacace, María José Robles-Frías, Maja Narlik-Grassow, Carmen Blanco-Aparicio, Amancio Carnero
The PIM family of serine/threonine kinases has three highly conserved isoforms (PIM1, PIM2 and PIM3). PIM proteins are regulated through transcription and stability by JAK/STAT pathways and are overexpressed in hematological malignancies and solid tumors. The PIM kinases possess weak oncogenic abilities, but enhance other genes or chemical carcinogens to induce tumors. We generated conditional transgenic mice that overexpress PIM1 or PIM2 in male reproductive organs and analyzed their contribution to tumorigenesis...
November 30, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27899802/genomic-and-transcriptional-landscape-of-p2ry8-crlf2-positive-childhood-acute-lymphoblastic-leukemia
#9
C Vesely, C Frech, C Eckert, G Cario, A Mecklenbräuker, U Zur Stadt, K Nebral, F Kraler, S Fischer, A Attarbaschi, M Schuster, C Bock, H Cavé, A von Stackelberg, M Schrappe, M A Horstmann, G Mann, O A Haas, R Panzer-Grümayer
Children with P2RY8-CRLF2-positive ALL have an increased relapse risk. Their mutational and transcriptional landscape as well as the respective patterns at relapse remains largely elusive. We therefore performed an integrated analysis of whole-exome and RNA-sequencing in 41 major clone fusion-positive cases including 19 matched diagnosis/relapse pairs. We detected a variety of frequently subclonal and highly instable JAK/STAT but also RTK/Ras pathway activating mutations in 76% of cases at diagnosis and virtually all relapses...
November 30, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27895788/effects-of-microrna-21-on-the-biological-functions-of-t-cell-acute-lymphoblastic-lymphoma-leukemia
#10
Cunzhen Shi, Xudong Zhang, Xin Li, Lei Zhang, Ling Li, Zhenchang Sun, Xiaorui Fu, Jingjing Wu, Yu Chang, Wencai Li, Qingjiang Chen, Mingzhi Zhang
Previous studies have demonstrated that microRNA-21 (miR-21) is an oncogene and is significantly upregulated in tumor tissue. However, its association with T-cell acute lymphoblastic lymphoma/leukemia (T-ALL) remains poorly understood. The aim of the present study was to investigate the effects of miR-21 on T-ALL cells by constructing Jurkat cells infected with recombinant adenovirus adv-miR-21 or adv-anti-miR-21. In addition, the target gene of miR-21 was identified by reverse transcription-quantitative polymerase chain reaction and western blotting...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27894770/activity-based-targeting-of-secretory-phospholipase-a2-enzymes-a-fatty-acid-binding-protein-assisted-approach
#11
Amir Keshavarz, Ligia Zelaya, Jasmeet Singh, Radha Ranganathan, Joseph Hajdu
Syntheses and enzymological characterization of fluorogenic substrate probes targeting secretory phospholipase A2 (sPLA2) for detection and quantitative assays are presented. Three fluorogenic phosphatidylcholine analogs PC-1, PC-2, and PC-3 each containing the duo of 7-mercapto-4-methyl-coumarin fluorophore and 2,4-dinitroanaline quencher on either tail were synthesized from (R)-3-amino-1,2-propanediol and R-(-)-2,2-dimethyl-1,3-dioxolane-4-methanol. These small reporter groups are advantageous in preserving natural membrane integrity...
November 25, 2016: Chemistry and Physics of Lipids
https://www.readbyqxmd.com/read/27894402/hsp90-inhibitor-enhances-anti-proliferative-and-apoptotic-effects-of-celecoxib-on-ht-29-colorectal-cancer-cells-via-increasing-bax-bcl-2-ratio
#12
A Mohammadi, M M Yaghoobi, A GholamhoseynianNajar, B Kalantari-Khandani, H Sharifi, M Saravani
Due to the high prevalence and mortality rate of colorectal cancer (CRC), new treatment approaches like combination therapy seem to be necessary. The relationship between chronic inflammation and colorectal cancer development and progression has been shown to be important. Celecoxib, a selective COX-2 inhibitor, is the only non-steroidal anti-inflammatory drug (NSAID) that has been approved for cancer therapy and prevention. Because of cardiovascular side effects of COX-2 inhibitors, combination therapy may improve the therapeutic profile...
October 31, 2016: Cellular and Molecular Biology
https://www.readbyqxmd.com/read/27890885/medication-adherence-improvement-by-using-administration-timing-simplification-protocol-atsp-in-cardiovascular-disease-patients
#13
Sun Hoi Jung, Ok Sang Lee, Hyang Sook Kim, Chan Soon Park, Hyun Jung Lee, Kyeng Hee Kwon, Hae Young Lee
AIMS: In chronic diseases, keeping adherence to medication is very difficult. The objective of this study was to evaluate the impact of administration timing simplification protocol (ATSP) on medication adherence and clinical parameters of cardiovascular diseases. METHODS: 210 out-patients with cardiovascular disease, who were taking two or more pills of any type of medication per day for more than one year, were enrolled and randomized. The intervention group followed the simplified administration schedule of ATSP with two main strategies: 1) moving medication from "pc" (30 minute after meal) to "stat...
November 25, 2016: Journal of Atherosclerosis and Thrombosis
https://www.readbyqxmd.com/read/27889106/expression-of-the-jak-stat-signaling-pathway-in-the-ligamentum-flavum-of-patients-with-lumbar-spinal-canal-stenosis
#14
Hitoshi Yamahata, Koji Osuka, Tatsuro Aoyama, Muneyoshi Yasuda, Hiroshi Tokimura, Kazunori Arita, Masakazu Takayasu
BACKGROUND: Ligamentum flavum (LF) hypertrophy is an important cause of lumbar spinal canal stenosis (LSS), one of the most common spinal disorders in the elderly. Although many cytokines are reported to be associated with LF hypertrophy, the intracellular signaling system is rarely discussed. The purpose of this study was to identify the JAK/STAT signaling pathway and to examine the role of the JAK/STAT systems in the hypertrophied LF. METHODS: The LF of 10 LSS patients was analyzed and the expression of JAK1, STAT3, phosphorylated (p)-STAT3, and actin was examined by Western blot analysis...
November 23, 2016: Journal of Orthopaedic Science: Official Journal of the Japanese Orthopaedic Association
https://www.readbyqxmd.com/read/27888751/remote-ischemic-preconditioning-attenuates-egr-1-expression-following-myocardial-ischemia-reperfusion-injury-through-activation-of-the-jak-stat-pathway
#15
H Mudaliar, B Rayner, M Billah, N Kapoor, W Lay, A Dona, R Bhindi
BACKGROUND/OBJECTIVES: Remote ischemic preconditioning (RIPC) protects the myocardium from ischemia/reperfusion (I/R) injury however the molecular pathways involved in cardioprotection are yet to be fully delineated. Transcription factor Early growth response-1 (Egr-1) is a key upstream activator in a variety of cardiovascular diseases. In this study, we elucidated the role of RIPC in modulating the regulation of Egr-1. METHODS: This study subjected rats to transient blockade of the left anterior descending (LAD) coronary artery with or without prior RIPC of the hind-limb muscle and thereafter excised the heart 24h following surgical intervention...
November 10, 2016: International Journal of Cardiology
https://www.readbyqxmd.com/read/27888688/an-oral-hemokine-tm-%C3%AE-methylhydrocinnamate-enhances-myeloid-and-neutrophil-recovery-following-irradiation-in-vivo
#16
Douglas V Faller, Serguei A Castaneda, Daohong Zhou, Merriline Vedamony, Peter E Newburger, Gary L White, Stanley Kosanke, P Artur Plett, Christie M Orschell, Michael S Boosalis, Susan P Perrine
An oral therapeutic which reduces duration of cytopenias and is active following accidental radiation exposures is an unmet need in radiation countermeasures. Alpha methylhydrocinnamate (ST7) prolongs STAT-5 phosphorylation, reduces growth-factor dependency of multi-lineage cell lines, and stimulates erythropoiesis. Here, ST7 and its isomers were studied for their effects on myeloid progenitors and hematopoietic stem cells (HSCs) following radiation, in nonhuman primates, and murine irradiation models. Addition of ST7 or ST7-S increased CFU-GM production by 1...
October 31, 2016: Blood Cells, Molecules & Diseases
https://www.readbyqxmd.com/read/27888216/drosophila-sulf1-is-required-for-the-termination-of-intestinal-stem-cell-division-during-regeneration
#17
Masahiko Takemura, Hiroshi Nakato
Stem cell division is activated to trigger regeneration in response to tissue damage. The molecular mechanisms by which this stem cell mitotic activity is properly repressed at the end of regeneration are poorly understood. Here we show that a specific modification of heparan sulfate (HS) is critical in regulating Drosophila intestinal stem cell (ISC) division during normal midgut homeostasis and regeneration. Loss of the extracellular HS endosulfatase Sulf1 results in increased ISC division during normal homeostasis, which is caused by upregulation of mitogenic signaling including the JAK/STAT, EGFR, and Hedgehog pathways...
November 25, 2016: Journal of Cell Science
https://www.readbyqxmd.com/read/27885302/cancers-of-the-thyroid-overview-and-statistics-in-the-united-states-and-oklahoma
#18
Munim H Deen, Kaitlin M Burke, Amanda Janitz, Janis Campbell
Recent studies have shown an apparent increase in thyroid cancer in the United States. Whether is due to an actual increase or increased screening is disputed. We analyzed thyroid cancer incidence and mortality across age and racial groups in Oklahoma (using data from the Oklahoma Central Cancer Registry) against Surveillance, Epidemiology, and End Results (SEER) program national data - using SEER*Stat software for mortality. In the US and Oklahoma, females had a higher AAIR compared to males, but it was lower in Oklahoma than in the US (Females: US 15...
July 2016: Journal of the Oklahoma State Medical Association
https://www.readbyqxmd.com/read/27884974/from-leeches-to-personalized-medicine-evolving-concepts-in-the-management-of-polycythemia-vera
#19
Alessandro Maria Vannucchi
Polycythemia vera (PV), a clonal disorders of hematopoietic stem/progenitor cells that manifests with prevalent expansion of red cell mass, is the most frequent among chronic myeloproliferative neoplasms (MPN). It is characterized by a V617F point mutation in JAK2 exon 14 , or less common mutations in exon 12, in virtually all cases. The landmark discovery of autonomously activated JAK/STAT signaling pathway paved the way for the clinical development of the first target drug, the JAK1 and JAK2 inhibitor ruxolitinib, that is now approved for patients with resistance or intolerance to hydroxyurea...
November 24, 2016: Haematologica
https://www.readbyqxmd.com/read/27884555/after-10years-of-jak2v617f-disease-biology-and-current-management-strategies-in-polycythaemia-vera
#20
REVIEW
Jacob Grinfeld, Anna L Godfrey
The JAK2V617F mutation accounts for the vast majority of patients with polycythaemia vera (PV) and around half of those with other Philadelphia-negative myeloproliferative neoplasms. Since its discovery in 2005, numerous insights have been gained into the pathways by which JAK2V617F causes myeloproliferation, including activation of JAK-STAT signalling but also through other canonical and non-canonical pathways. A variety of mechanisms explain how this one mutation can be associated with distinct clinical disorders, demonstrating how constitutional and acquired factors may interact in the presence of a single mutation to determine disease phenotype...
November 15, 2016: Blood Reviews
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