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https://www.readbyqxmd.com/read/27919641/effect-of-hyperthyroidism-on-circulating-prolactin-and-hypothalamic-expression-of-tyrosine-hydroxylase-prolactin-signaling-cascade-members-and-estrogen-and-progesterone-receptors-during-late-pregnancy-and-lactation-in-the-rat
#1
Gisela E Pennacchio, Flavia J Neira, Marta Soaje, Graciela A Jahn, Susana R Valdez
Hyperthyroidism (HyperT) compromises pregnancy and lactation, hindering suckling-induced PRL release. We studied the effect of HyperT on hypothalamic mRNA (RT-qPCR) and protein (Western blot) expression of tyrosine hydroxylase (TH), PRL receptor (PRLR) and signaling pathway members, estrogen-α (ERα) and progesterone (PR) receptors on late pregnancy (days G19, 20 and 21) and early lactation (L2) in rats. HyperT advanced pre-partum PRL release, reduced circulating PRL on L2 and increased TH mRNA (G21 and L2), p-TH, PRLR mRNA, STAT5 protein (G19 and L2), PRLR protein (G21) and CIS protein (G19)...
December 2, 2016: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/27901054/functional-defects-in-cd4-cd25-high-foxp3-regulatory-cells-in-ankylosing-spondylitis
#2
Huifang Guo, Ming Zheng, Kui Zhang, Fengfan Yang, Xin Zhang, Qing Han, Zhi-Nan Chen, Ping Zhu
Forkhead box P3 (FoxP3)-positive regulatory T cells (Tregs) play a pivotal role in the preservation of self-tolerance, and Treg dysfunction has been implicated in many autoimmune diseases. Whether and how Tregs participate in the pathogenesis of ankylosing spondylitis (AS) has not been fully elucidated. Here, we investigated Treg function and found that Tregs in peripheral blood (PB) from patients with active AS had lower FoxP3 mean fluorescence intensity (MFI) than those from healthy controls and could not fully suppress naïve T cell (Tn) proliferation...
November 30, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27899224/interleukin-7-and-15-maintain-pathogenic-memory-th17-cells-in-autoimmunity
#3
Yihe Chen, Sunil K Chauhan, Xuhua Tan, Reza Dana
Th17 cells are principal mediators of many autoimmune conditions. Recently, memory Th17 cells have been revealed as crucial in mediating the chronicity of various refractory autoimmune disorders; however, the underlying mechanisms maintaining memory Th17 cells have remained elusive. Here, using a preclinical model of ocular autoimmune disease we show that both IL-7 and IL-15 are critical for maintaining pathogenic memory Th17 cells. Neutralization of these cytokines leads to substantial reduction of memory Th17 cells; both IL-7 and IL-15 provide survival signals via activating STAT5, and IL-15 provides additional proliferation signals via activating both STAT5 and Akt...
November 26, 2016: Journal of Autoimmunity
https://www.readbyqxmd.com/read/27892697/allium-roseum-l-extract-exerts-potent-suppressive-activities-on-chronic-myeloid-leukemia-k562-cell-viability-through-the-inhibition-of-bcr-abl-pi3k-akt-and-erk1-2-pathways-and-the-abrogation-of-vegf-secretion
#4
Soumaya Souid, Hanen Najjaa, Ichrak Riahi-Chebbi, Meriam Haoues, Mohamed Neffati, Ingrid Arnault, Jacques Auger, Habib Karoui, Makram Essafi, Khadija Essafi-Benkhadir
Use of plant extracts, alone or combined to the current chemotherapy as chemosensitizers, has emerged as a promising strategy to overcome tumor drug resistance. Here, we investigated the anticancer activity of Allium roseum L. extracts, a wild edible species in North Africa, on human Chronic Myeloid Leukemia (CML) K562 cells. The dehydrated aqueous extract (DAE) disturbed the cell cycle progression and induced the apoptosis of K562 cells. Chemical analysis of DAE showed a diversity of organosulfur compounds S-alk(en)yl-cysteine sulfoxides (RCSO) and high amount of allicin, suggesting that such molecule may be behind its antitumor effect...
November 28, 2016: Nutrition and Cancer
https://www.readbyqxmd.com/read/27879203/fetal-and-neonatal-hematopoietic-progenitors-are-functionally-and-transcriptionally-resistant-to-flt3-itd-mutations
#5
Shaina N Porter, Andrew S Cluster, Wei Yang, Kelsey A Busken, Riddhi M Patel, Jiyeon A Ryoo, Jeffrey A Magee
The FLT3 Internal Tandem Duplication (FLT3(ITD)) mutation is common in adult acute myeloid leukemia (AML) but rare in early childhood AML. It is not clear why this difference occurs. Here we show that Flt3(ITD) and cooperating Flt3(ITD)/Runx1 mutations cause hematopoietic stem cell depletion and myeloid progenitor expansion during adult but not fetal stages of murine development. In adult progenitors, FLT3(ITD) simultaneously induces self-renewal and myeloid commitment programs via STAT5-dependent and STAT5-independent mechanisms, respectively...
November 23, 2016: ELife
https://www.readbyqxmd.com/read/27858144/th9-and-other-il-9-producing-cells-in-allergic-asthma
#6
REVIEW
Sonja Koch, Nina Sopel, Susetta Finotto
Allergic asthma is a worldwide increasing chronic disease of the airways which affects more than 300 million people. It is associated with increased IgE, mast cell activation, airway hyperresponsiveness (AHR), mucus overproduction and remodeling of the airways. Previously, this pathological trait has been associated with T helper type 2 (Th2) cells. Recently, different CD4(+) T cell subsets (Th17, Th9) as well as cells of innate immunity, like mast cells and innate lymphoid cells type 2 (ILC2s), which are all capable of producing the rediscovered cytokine IL-9, are known to contribute to this disease...
November 17, 2016: Seminars in Immunopathology
https://www.readbyqxmd.com/read/27858140/adipocyte-stat5-deficiency-promotes-adiposity-and-impairs-lipid-mobilisation-in-mice
#7
Doris Kaltenecker, Kristina M Mueller, Pia Benedikt, Ursula Feiler, Madeleine Themanns, Michaela Schlederer, Lukas Kenner, Martina Schweiger, Guenter Haemmerle, Richard Moriggl
AIMS/HYPOTHESIS: Dysfunction of lipid metabolism in white adipose tissue can substantially interfere with health and quality of life, for example in obesity and associated metabolic diseases. Therefore, it is important to characterise pathways that regulate lipid handling in adipocytes and determine how they affect metabolic homeostasis. Components of the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway are involved in adipocyte physiology and pathophysiology...
November 17, 2016: Diabetologia
https://www.readbyqxmd.com/read/27856601/axl-blockade-by-bgb324-inhibits-bcr-abl-tyrosine-kinase-inhibitor-sensitive-and-resistant-chronic-myeloid-leukemia
#8
Isabel Ben Batalla, Robert Erdmann, Heather Jørgensen, Rebecca Mitchell, Thomas Ernst, Gunhild von Amsberg, Philippe Schafhausen, Janna L Velthaus, Stephen Rankin, Richard E Clark, Steffen Koschmieder, Alexander Schultze, Subir Mitra, Peter Vandenberghe, Tim H Brümmendorf, Peter Carmeliet, Andreas Hochhaus, Klaus Pantel, Carsten Bokemeyer, G Vignir Helgason, Tessa L Holyoake, Sonja Loges
PURPOSE: BCR-ABL kinase inhibitors are employed successfully for chronic myeloid leukemia (CML) treatment. However, resistant disease and persistence of BCR-ABL1-independent leukemia stem and progenitor cells (LSPC) remain clinical challenges. The receptor tyrosine kinase Axl can mediate survival and therapy resistance of different cancer cells. We investigated the therapeutic potential of Axl inhibition in CML. EXPERIMENTAL DESIGN: We used primary cells from CML patients and TKI-sensitive and -resistant BCR-ABL1+ CML cell lines and a novel Ponatinib-resistant cell line KCL-22 PonR...
November 17, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27855183/interleukins-7-and-15-maintain-human-t-cell-proliferative-capacity-through-stat5-signaling
#9
Adam Drake, Mandeep Kaur, Bettina P Iliopoulou, Ryan Phennicie, Amanda Hanson, Jianzhu Chen
T lymphocytes require signals from self-peptides and cytokines, most notably interleukins 7 and 15 (IL-7, IL-15), for survival. While mouse T cells die rapidly if IL-7 or IL-15 is withdrawn, human T cells can survive prolonged withdrawal of IL-7 and IL-15. Here we show that IL-7 and IL-15 are required to maintain human T cell proliferative capacity through the STAT5 signaling pathway. T cells from humanized mice proliferate better if stimulated in the presence of human IL-7 or IL-15 or if T cells are exposed to human IL-7 or IL-15 in mice...
2016: PloS One
https://www.readbyqxmd.com/read/27853239/antagonizing-stat5b-dimerization-with-an-osmium-complex
#10
Li-Juan Liu, Wanhe Wang, Tian-Shu Kang, Jia-Xin Liang, Chenfu Liu, Daniel W J Kwong, Vincent Kam Wai Wong, Dik-Lung Ma, Chung-Hang Leung
Targeting STAT5 is an appealing therapeutic strategy for the treatment of hematologic malignancies and inflammation. Here, we present the novel osmium(II) complex 1 as the first metal-based inhibitor of STAT5B dimerization. Complex 1 exhibited superior inhibitory activity against STAT5B DNA binding compared to STAT5A DNA binding. Moreover, 1 repressed STAT5B transcription and blocked STAT5B dimerization via binding to the STAT5B protein, thereby inhibiting STAT5B translocation to the nucleus. Furthermore, 1 was able to selectively inhibit STAT5B phosphorylation without affecting the expression level of STAT5B...
November 17, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27852740/temporal-expression-of-bim-limits-the-development-of-agonist-selected-thymocytes-and-skews-their-tcr%C3%AE-repertoire
#11
Kun-Po Li, Anke Fähnrich, Eron Roy, Carla M Cuda, H Leighton Grimes, Harris R Perlman, Kathrin Kalies, David A Hildeman
CD8αα TCRαβ(+) intestinal intraepithelial lymphocytes play a critical role in promoting intestinal homeostasis, although mechanisms controlling their development and peripheral homeostasis remain unclear. In this study, we examined the spatiotemporal role of Bim in the thymic selection of CD8αα precursors and the fate of these cells in the periphery. We found that T cell-specific expression of Bim during early/cortical, but not late/medullary, thymic development controls the agonist selection of CD8αα precursors and limits their private TCRβ repertoire...
November 16, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27821177/hepatitis-b-virus-x-protein-promotes-interleukin-7-receptor-expression-via-nf-%C3%AE%C2%BAb-and-notch1-pathway-to-facilitate-proliferation-and-migration-of-hepatitis-b-virus-related-hepatoma-cells
#12
Fanyun Kong, Wei Hu, Kai Zhou, Xiao Wei, Yanbo Kou, Hongjuan You, Kuiyang Zheng, Renxian Tang
BACKGROUND: Interleukin-7 receptor (IL-7R) is involved in the abnormal function of solid tumors, but the role and regulatory mechanisms of IL-7R in HBV-related hepatocellular carcinoma (HCC) are still unclear. METHODS: Gene and protein expression levels of IL-7R were examined in hepatoma cells transfected with hepatitis B virus (HBV) plasmids and in hepatoma cells transfected with the multifunctional nonstructural protein X (HBX). The expression of HBX and IL-7R was measured by immunohistochemical analysis in HBV-related HCC tissues...
November 7, 2016: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/27816761/deletion-of-liver-specific-stat5-gene-alters-the-expression-of-bile-acid-metabolism-genes-and-reduces-liver-damage-in-lithogenic-diet-fed-mice
#13
Myunggi Baik, Jangseon Kim, Min Yu Piao, Hyeok Joong Kang, Seung Ju Park, Sang Weon Na, Sung-Hoon Ahn, Jae-Hyuk Lee
Signal transducers and activators of transcription 5 (STAT5) mediates growth hormone signals, which may control hepatic cholesterol uptake and bile acid metabolism. Deregulation of liver cholesterol homeostasis and bile acid metabolism may cause liver damage and cholesterol gallstone development. The purpose of this study was to understand the role of local STAT5 signaling in cholesterol and bile acid metabolism using liver-specific STAT5 knock-out (STAT5 LKO) mice on a normal diet and a cholesterol- and bile acid-containing lithogenic diet...
January 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/27815912/intracellular-flow-cytometry-improvements-in-clinical-studies
#14
Julie Demaret, Morgane Gossez, Fabienne Venet, Guillaume Monneret
Flow cytometry has become a basic of biological research and clinical diagnostics, and its application has been crucial to numerous advances in immunology and cell biology. However, several issues remain when considering intracellular stainings, especially in the context of a daily routine use and in multicenter clinical research protocols including large cohorts of patients. The requirements for multiple protocol steps are not only time-consuming but also frequently associated with high cell loss and nonspecific binding or reduced fluorescence...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27815198/comparative-immunity-of-salmo-salar-and-oncorhynchus-kisutch-during-infestation-with-the-sea-louse-caligus-rogercresseyi-an-enrichment-transcriptome-analysis
#15
Valentina Valenzuela-Muñoz, Sebastian Boltaña, Cristian Gallardo-Escárate
Caligus rogercresseyi, an ectoparasite affecting the Chilean salmon industry, can cause immunosuppression and physiological stress in farmed fish. Interestingly, coho salmon (Oncorhynchus kisutch) are notably resistant to infestation, whereas Atlantic salmon (Salmo salar) are phenotypically more susceptible to sea lice. However, comparative studies on immune responses to C. rogercresseyi have not been conducted. In this study, Illumina sequencing was conducted to evaluate head kidney and skin samples taken 7 and 14 days post-infestation, yielding a total of 1492 and 1522 contigs annotated to immune-related genes for Atlantic and coho salmon, respectively...
December 2016: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/27812545/low-dose-il-2-selectively-activates-subsets-of-cd4-tregs-and-nk-cells
#16
Masahiro Hirakawa, Tiago Matos, Hongye Liu, John Koreth, Haesook T Kim, Nicole E Paul, Kazuyuki Murase, Jennifer Whangbo, Ana C Alho, Sarah Nikiforow, Corey Cutler, Vincent T Ho, Philippe Armand, Edwin P Alyea, Joseph H Antin, Bruce R Blazar, Joao F Lacerda, Robert J Soiffer, Jerome Ritz
CD4(+) regulatory T cells (CD4Tregs) play a critical role in the maintenance of immune tolerance and prevention of chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation. IL-2 supports the proliferation and survival of CD4Tregs and previous studies have demonstrated that IL-2 induces selective expansion of CD4Tregs and improves clinical manifestations of chronic GVHD. However, mechanisms for selective activation of CD4Tregs and the effects of low-dose IL-2 on other immune cells are not well understood...
November 3, 2016: JCI Insight
https://www.readbyqxmd.com/read/27812285/a-multifaceted-role-for-myd88-dependent-signaling-in-progression-of-murine-mammary-carcinoma
#17
Mary J Higgins, Antonio Serrano, Kofi Y Boateng, Victoria A Parsons, Tiffany Phuong, Alyssa Seifert, Jacob M Ricca, Kyle C Tucker, Alec S Eidelman, Maureen A Carey, Robert A Kurt
Previous data obtained in our laboratory suggested that there may be constitutive signaling through the myeloid differentiation primary response gene 88 (Myd88)-dependent signaling cascade in murine mammary carcinoma. Here, we extended these findings by showing that, in the absence of an added Toll-like receptor (TLR) agonist, the myddosome complex was preformed in 4T1 tumor cells, and that Myd88 influenced cytoplasmic extracellular signal-regulated kinase (Erk)1/Erk2 levels, nuclear levels of nuclear factor-kappaB (NFκB) and signal transducer and activator of transcription 5 (STAT5), tumor-derived chemokine (C-C motif) ligand 2 (CCL2) expression, and in vitro and in vivo tumor growth...
2016: Breast Cancer: Basic and Clinical Research
https://www.readbyqxmd.com/read/27807369/calreticulin-mutant-mice-develop-essential-thrombocythemia-that-is-ameliorated-by-the-jak-inhibitor-ruxolitinib
#18
K Shide, T Kameda, T Yamaji, M Sekine, N Inada, A Kamiunten, K Akizuki, K Nakamura, T Hidaka, Y Kubuki, H Shimoda, A Kitanaka, A Honda, A Sawaguchi, H Abe, T Miike, H Iwakiri, Y Tahara, M Sueta, S Hasuike, S Yamamoto, K Nagata, K Shimoda
Mutations of calreticulin (CALR) are detected in 25-30% of patients with essential thrombocythemia (ET) or primary myelofibrosis and cause frameshifts that result in proteins with a novel C-terminal. We demonstrate that CALR mutations activated signal transducer and activator of transcription 5 (STAT5) in 293T cells in the presence of thrombopoietin receptor (MPL). Human megakaryocytic CMK11-5 cells and erythroleukemic F-36P-MPL cells with knocked-in CALR mutations showed increased growth and acquisition of cytokine-independent growth, respectively, accompanied by STAT5 phosphorylation...
November 29, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27799311/acetylation-modulates-il-2-receptor-signaling-in-t-cells
#19
Taku Kuwabara, Hirotake Kasai, Motonari Kondo
Ligand binding to the cognate cytokine receptors activates intracellular signaling by recruiting protein tyrosine kinases and other protein modification enzymes. However, the roles of protein modifications other than phosphorylation remain unclear. In this study, we examine a novel regulatory mechanism of Stat5, based on its acetylation. As for phosphorylation, IL-2 induces the acetylation of signaling molecules, including Stat5, in the murine T cell line CTLL-2. Stat5 is acetylated in the cytoplasm by CREB-binding protein (CBP)...
October 31, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27791988/dysregulated-expression-of-micrornas-and-mrnas-in-pulmonary-artery-remodeling-in-ascites-syndrome-in-broiler-chickens
#20
Ping Liu, Fei Yang, Yu Zhuang, Qingyang Xiao, Huabin Cao, Caiying Zhang, Tiancheng Wang, Huayuan Lin, Xiaoquan Guo, Guoliang Hu
Ascites syndrome (AS), also known as pulmonary artery hypertension, remains a challenging disease that severely affects both humans and broiler chickens. Pulmonary artery remodeling presents a key step in the development of AS. In this study, we obtained pulmonary artery tissues from broilers with and without AS to perform miRNA sequencing analysis, miRNA-mRNA association analysis and pathological examinations. 29 significantly differentially expressed miRNAs were found both in known and novel miRNAs with 18 up-regulated and 11 down-regulated miRNAs...
October 25, 2016: Oncotarget
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