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https://www.readbyqxmd.com/read/28735449/therapy-with-omeprazole-modulates-regulatory-t-cell-t-helper-17-immune-response-in-children-with-duodenal-ulcers
#1
Chuan-Ying Li, Cheng Wu
The purpose of this study was to determine the effect of omeprazole on the regulatory T cell (Treg) and T helper 17 (Th17)-mediated response in patients with duodenal ulcers (DUs). DU patients were randomly divided into omeprazole and colloid bismuth subcitrate treatment groups. The ratios of Th17 and Treg in peripheral blood mononuclear cells (PBMCs) were measured. Cytokine production and Foxp3(+)- and RORγt-positive cells were detected. The expressions of STAT3, p-STAT3, STAT5 and p-STAT5 were detected by Western blot...
July 22, 2017: Inflammopharmacology
https://www.readbyqxmd.com/read/28713977/analysis-of-gene-expression-profile-microarray-data-in-complex-regional-pain-syndrome
#2
Wulin Tan, Yiyan Song, Chengqiang Mo, Shuangjian Jiang, Zhongxing Wang
The aim of the present study was to predict key genes and proteins associated with complex regional pain syndrome (CRPS) using bioinformatics analysis. The gene expression profiling microarray data, GSE47603, which included peripheral blood samples from 4 patients with CRPS and 5 healthy controls, was obtained from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) in CRPS patients compared with healthy controls were identified using the GEO2R online tool. Functional enrichment analysis was then performed using The Database for Annotation Visualization and Integrated Discovery online tool...
September 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28713936/epigallocatechin-gallate-attenuates-overload%C3%A2-induced-cardiac-ecm-remodeling-via-restoring-t-cell-homeostasis
#3
Yongsheng Han, Qingtong Wang, Xizhen Fan, Jun Chu, Junfu Peng, Yousheng Zhu, Yan Li, Xiaojing Li, Lei Shen, James Asenso, Shanfeng Li
It has previously been demonstrated that Epigallocatechin gallate (EGCG) has regulatory effects on cellular immunity. The present study explored whether EGCG inhibits the overload‑induced cardiac extracellular matrix (ECM) remodeling through targeting the balance of T cell subpopulations. Sprague‑Dawley rats were subjected to either transverse aortic constriction (TAC) or sham operation. TAC rats were treated with EGCG or valsartan (Val) for 6 weeks. The administration of EGCG or Val ameliorated the overproduction of cardiac collagen, inhibited matrix metalloproteinase (MMP) activity, decreased the expression of tissue inhibitor of MMP‑2, atrial natriuretic peptide and brain natriuretic peptide...
September 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28713870/il-10-induces-a-stat3-dependent-autoregulatory-loop-in-th2-cells-that-promotes-blimp-1-restriction-of-cell-expansion-via-antagonism-of-stat5-target-genes
#4
Amanda C Poholek, Dragana Jankovic, Alejandro V Villarino, Franziska Petermann, Angela Hettinga, Dror S Shouval, Scott B Snapper, Susan M Kaech, Stephen R Brooks, Golnaz Vahedi, Alan Sher, Yuka Kanno, John J O'Shea
Blimp-1 expression in T cells extinguishes the fate of T follicular helper cells, drives terminal differentiation, and limits autoimmunity. Although various factors have been described to control Blimp-1 expression in T cells, little is known about what regulates Blimp-1 expression in T helper 2 (TH2) cells and the molecular basis of its actions. We report that signal transducer and activator of transcription 3 (STAT3) unexpectedly played a critical role in regulating Blimp-1 in TH2 cells. Furthermore, we found that the cytokine interleukin-10 (IL-10) acted directly on TH2 cells and was necessary and sufficient to induce optimal Blimp-1 expression through STAT3...
October 2016: Science Immunology
https://www.readbyqxmd.com/read/28713437/astragalus-extract-mixture-ht042-increases-longitudinal-bone-growth-rate-by-upregulating-circulatory-igf-1-in-rats
#5
Donghun Lee, Sung Hyun Lee, Yoon Hee Lee, Jungbin Song, Hocheol Kim
Astragalus extract mixture HT042 is a standardized ingredient of health functional food approved by Korean FDA with a claim of "height growth of children." HT042 stimulates bone growth rate and increases local IGF-1 expression in growth plate of rats which can be considered as direct stimulation of GH and its paracrine/autocrine actions. However, it remains unclear whether HT042 stimulates circulatory IGF-1 which also plays a major role to stimulate bone growth. To determine the effects on circulatory IGF-1, IGF-1 and IGFBP-3 expressions and phosphorylation of JAK2/STAT5 were evaluated in the liver after 10 days of HT042 administration...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28712960/mrtf-a-mediated-fn-and-icam-1-expression-in-ages-induced-rat-glomerular-mesangial-cells-via-activating-stat5
#6
Qiuhong Chen, Junying Huang, Wenyan Gong, Zhiquan Chen, Jiani Huang, Peiqing Liu, Heqing Huang
Advanced glycation end products (AGEs), formed at an accelerated rate under diabetes, play a role in inflammation and fibrosis in mesangial areas in diabetic nephropathy (DN). However, the transcriptional modulator that mediates the cellular response to AGEs remains largely obscure. Our goal was to determine whether myocardin-related transcription factor (MRTF)-A, a key protein involved in the transcriptional regulation of smooth muscle cell phenotype, was responsible for the glomerular mesangial cells (GMCs) injury by AGEs, and, if so, how MRTF-A promoted mesangial dysfunction initiated by AGEs...
July 13, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28705432/identification-of-galiellalactone-based-novel-stat3-selective-inhibitors-with-cytotoxic-activities-against-triple-negative-breast-cancer-cell-lines
#7
Hyun Su Kim, Taewoo Kim, Hyejin Ko, Jeeyeon Lee, Yeong Shik Kim, Young-Ger Suh
Signal transducer and activator of transcription 3 (STAT3) is phosphorylated in breast cancer cells, particularly triple-negative breast cancers (TNBCs). Therefore, the inhibition of constitutive phosphorylated STAT3 is a promising therapeutic for TNBC treatment. Recently, a series of novel STAT3 inhibitors based on natural (-)-galiellalactone have been identified to inhibit STAT3 phosphorylation at the Tyr705 residue. Interestingly, the truncation of the cyclohexene moiety of (-)-galiellalactone to [3.3] bicyclic lactone as a pharmacophoric core produced improved cytotoxic effects against TNBCs...
June 23, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28701509/dendritic-cell-derived-il-32%C3%AE-a-novel-inhibitory-cytokine-of-nk-cell-function
#8
Laurent Gorvel, Daniel Korenfeld, Thomas Tung, Eynav Klechevsky
Cytokines produced by dendritic cells (DCs) can largely determine the direction of immunity. Transcriptional analysis revealed that besides IL-15, IL-32 was the only other cytokine expressed by human Langerhans cells. IL-32 is a human cytokine that exists in four main isoforms. Currently, little is known about the regulation and function of the various IL-32 isoforms. In this study, we found that IL-15 is a potent inducer of IL-32α in DCs. Because IL-15 promotes NK cell activation, we investigated the interplay between IL-32 and IL-15 and their role in NK cell activity...
July 12, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28694329/feminization-of-male-mouse-liver-by-persistent-growth-hormone-stimulation-activation-of-sex-biased-transcriptional-networks-and-dynamic-changes-in-chromatin-states
#9
Dana Lau-Corona, Alexander Suvorov, David J Waxman
Sex-dependent pituitary GH secretory profiles--pulsatile in males and persistent in females--regulate sex-biased, STAT5-dependent expression of hundreds of genes in mouse liver, imparting sex differences in hepatic drug/lipid metabolism and disease risk. Here we examine transcriptional and epigenetic changes induced by continuous-GH infusion (cGH) in male mice, which rapidly feminizes the temporal profile of liver STAT5 activity. cGH repressed 86% of male-biased genes and induced 68% of female-biased genes within 4-days; however, several highly female-specific genes showed weak or no feminization, even after 14-days cGH...
July 10, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28692941/fibroblast-growth-factor-21-ameliorates-high-glucose-induced-fibrogenesis-in-mesangial-cells-through-inhibiting-stat5-signaling-pathway
#10
Shuai Li, Xiaochen Guo, Teng Zhang, Nan Wang, Junyan Li, Pengfei Xu, Shengqi Zhang, Guiping Ren, Deshan Li
Fibroblast growth factor 21 (FGF21) is a member of the FGF family and acts as a potent regulator of glucose and lipid homeostasis, but its effect on renal fibrosis and the underlying mechanisms are totally unknown. The purpose of this study was designed to investigate whether FGF21 has effect on high glucose-induced fibrogenesis in human mesangial cells (HMCs) and the underlying mechanism. High glucose is well known to stimulate the expression of extracelluar matrix (ECM) in human mesangial cells. In humans, overexpression and deposition of ECM lead to renal fibrosis...
July 7, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28692056/pdzk1-inhibits-the-development-and-progression-of-renal-cell-carcinoma-by-suppression-of-shp-1-phosphorylation
#11
T Tao, X Yang, J Zheng, D Feng, Q Qin, X Shi, Q Wang, C Zhao, Z Peng, H Liu, W G Jiang, J He
Renal cell carcinoma (RCC) is one of the most aggressive urologic cancers, however, the mechanism on supporting RCC carcinogenesis is still not clear. By using gene expression profile analysis and functional clustering, PDZ domain-containing 1 (PDZK1) was revealed to be downregulated in human clear cell renal cell carcinoma (ccRCC) samples, which was also verified in several independent public ccRCC data sets. Using PDZK1 overexpression and knockdown models in ccRCC cell lines, we demonstrated that PDZK1 inhibited cell proliferation, cell cycle G1/S phase transition, cell migration and invasion, indicating a tumor-suppressor role in the development and progression of ccRCC...
July 10, 2017: Oncogene
https://www.readbyqxmd.com/read/28686504/prolactin-and-oleic-acid-synergistically-stimulate-%C3%AE-cell-proliferation-and-growth-in-rat-islets
#12
Todd Clark Brelje, Nicholas V Bhagroo, Laurence E Stout, Robert L Sorenson
Islet adaptation to pregnancy is largely influenced by prolactin and placental lactogens. In addition serum lipids are significantly increased. Here, we report the novel observation that prolactin and oleic acid synergistically stimulate islet cell proliferation and islet growth. In neonatal rat islets, prolactin increased proliferation 6-fold, oleic acid 3.5-fold, and their combination 15-fold. The expression of insulin in these dividing cells establishes them as β-cells. Similar changes were seen in islet growth...
July 4, 2017: Islets
https://www.readbyqxmd.com/read/28684419/versican-g1-domain-enhances-adenoviral-mediated-transgene-expression-and-can-be-modulated-by-inhibitors-of-the-janus-kinase-jak-stat-and-src-family-kinase-pathways
#13
Patricia Y Akinfenwa, Wesley S Bond, Cristhian J Ildefonso, Mary Y Hurwitz, Richard L Hurwitz
To examine the biochemical influences that may contribute to the success of gene therapy for ocular disorders, the role of versican, a vitreous component, in adenoviral-mediated transgene expression was examined. Versican is a large chondroitin sulfate-containing, hyaluronic acid-binding proteoglycan present in the extracellular matrix and in ocular vitreous body. Y79 retinoblastoma cells and CD44-negative SK-N-DZ neuroblastoma cells transduced with adenoviral vectors in the presence of versican respond with an activation of transgene expression...
July 6, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28682943/remote-ischemic-post-conditioning-improves-myocardial-dysfunction-via-the-risk-and-safe-pathways-in-a-rat-model-of-severe-hemorrhagic-shock
#14
Jianrong Huang, Dawei Xu, Qinyue Guo, Bing Ou, Qin Ling, Jianhua Li, Zhengfei Yang, Wanchun Tang
INTRODUCTION: Patients who have been resuscitated after severe hemorrhagic shock still have a high mortality rate. Previously published literature has suggested that remote ischemic postconditioning (RIPostC) has a cardioprotective effect, but few studies have focused on RIPostC performed after severe hemorrhagic shock. In this study, we aim to explore the effects and mechanism of RIPostC on myocardial ischemia and reperfusion injuries after hemorrhagic shock. METHODS: Fifty male rats were randomized into four groups: Sham, Control, RIPerC (remote ischemic per-conditioning) and RIPostC...
July 4, 2017: Shock
https://www.readbyqxmd.com/read/28676702/extracellular-matrix-promotes-clathrin-dependent-endocytosis-of-prolactin-and-stat5-activation-in-differentiating-mammary-epithelial-cells
#15
Rebecca E Bridgewater, Charles H Streuli, Patrick T Caswell
The hormone prolactin promotes lactational differentiation of mammary epithelial cells (MECs) via its cognate receptor and the downstream JAK2-STAT5a signalling pathway. In turn this regulates transcription of milk protein genes. Prolactin signalling depends on a cross-talk with basement membrane extracellular matrix (ECM) via β1 integrins which activate both ILK and Rac1 and are required for STAT5a activation and lactational differentiation. Endocytosis is an important regulator of signalling. It can both enhance and suppress cytokine signalling, although the role of endocytosis for prolactin signalling is not known...
July 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28676638/cbl-mediated-k63-linked-ubiquitination-of-jak2-enhances-jak2-phosphorylation-and-signal-transduction
#16
Chun-Shan Liu, Hsin-Fang Yang-Yen, Ching-Shu Suen, Ming-Jing Hwang, Jeffrey Jong-Young Yen
JAK2 activation is crucial for cytokine receptor signal transduction and leukemogenesis. However, the underlying processes that lead to full activation of JAK2 are unclear. Here, we report a positive role for ubiquitination of JAK2 during GM-CSF-induced activation. Upon GM-CSF stimulation, JAK2 ubiquitination is significantly enhanced through K63-linked poly-ubiquitination. Studies employing both knockout and overexpression of Cbl, an E3 ubiquitin ligase, led to the conclusion that Cbl specifically promotes JAK2 ubiquitination, and this was further confirmed in vitro using a Cbl ubiquitination assay...
July 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28667329/imipramine-blue-sensitively-and-selectively-targets-flt3-itd-positive-acute-myeloid-leukemia-cells
#17
Jonathan Metts, Heath L Bradley, Zhengqi Wang, Neil P Shah, Reuben Kapur, Jack L Arbiser, Kevin D Bunting
Aberrant cytokine signaling initiated from mutant receptor tyrosine kinases (RTKs) provides critical growth and survival signals in high risk acute myeloid leukemia (AML). Inhibitors to FLT3 have already been tested in clinical trials, however, drug resistance limits clinical efficacy. Mutant receptor tyrosine kinases are mislocalized in the endoplasmic reticulum (ER) of AML and play an important role in the non-canonical activation of signal transducer and activator of transcription 5 (STAT5). Here, we have tested a potent new drug called imipramine blue (IB), which is a chimeric molecule with a dual mechanism of action...
June 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28657677/effects-of-pimozide-derivatives-on-pstat5-in-k562-cells
#18
Riccardo Rondanin, Daniele Simoni, Martina Maccesi, Romeo Romagnoli, Stefania Grimaudo, Rosaria Maria Pipitone, Maria Meli, Antonio Cascio, Manlio Tolomeo
STAT5 is a transcription factor, component of the STAT family of signalling proteins. STAT-5 is involved in many types of cancer, including chronic myelogenous leukemia (CML), where this protein is found constitutively activated as a consequence of the BCR-ABL expression. Recently, literature has reported that neuroleptic drug pimozide can act as inhibitor of STAT5 phosphorylation and is capable to induce apoptosis in CML cells in vitro. Our group has synthesized simple derivatives of pimozide, with cytotoxic activity and able to reduce the levels of phosphorylated STAT5...
June 28, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28654259/new-inhibitor-targeting-signal-transducer-and-activator-of-transcription-5-stat5-signaling-in-myeloid-leukemias
#19
Ludovic Juen, Marie Brachet-Botineau, Cécile Parmenon, Jérôme Bourgeais, Olivier Hérault, Fabrice Gouilleux, Marie-Claude Viaud-Massuard, Gildas Prié
Signal transducers and activators of transcription 5 (STAT5s) are crucial effectors of tyrosine kinase oncogenes in myeloid leukemias. Inhibition of STAT5 would contribute to reducing the survival of leukemic cells and also tackling their chemoresistance. In a first screening experiment, we identified hit 13 as able to inhibit STAT5 phosphorylation and leukemic cell growth. The synthesis of 18 analogues of 13 allowed us to identify one compound, 17f, as having the most potent antileukemic effect. 17f inhibited the growth of acute and chronic myeloid leukemia cells and the phosphorylation and transcriptional activity of STAT5...
July 12, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28638744/azacytidine-prevents-experimental-xenogeneic-graft-versus-host-disease-without-abrogating-graft-versus-leukemia-effects
#20
Grégory Ehx, Gilles Fransolet, Laurence de Leval, Stéphanie D'Hondt, Sophie Lucas, Muriel Hannon, Loïc Delens, Sophie Dubois, Pierre Drion, Yves Beguin, Stéphanie Humblet-Baron, Frédéric Baron
The demethylating agent 5-azacytidine (AZA) has proven its efficacy in the treatment of myelodysplastic syndrome and acute myeloid leukemia. In addition, AZA can demethylate FOXP3 intron 1 (FOXP3i1) leading to the generation of regulatory T cells (Treg). Here, we investigated the impact of AZA on xenogeneic graft-vs.-host disease (xGVHD) and graft-vs.-leukemia effects in a humanized murine model of transplantation (human PBMCs-infused NSG mice), and described the impact of the drug on human T cells in vivo...
2017: Oncoimmunology
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