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https://www.readbyqxmd.com/read/28109147/-co-culture-with-umbilical-cord-mesenchymal-stem-cells-promotes-the-synthesis-and-mechnism-of-milk-protein-in-bovine-mammary-epithelial-cells
#1
Yankun Zhao, Wei Shao, Chenglong Luo, Kaile Wu, Xiong Yu
Objective To explore the possible mechanism of umbilical cord mesenchymal stem cells (UCMSCs) regulating milk protein synthesis in bovine mammary gland epithelial cells (BMECs). Methods UCMSCs and BMECs were co-cultured by double-chamber Transwell(TM), and other BMECs were cultured alone as a control group. Insulin like growth factor 1 receptor (IGF-1R) inhibitor AG1024 was used to treat cells. IGF-1, β casein (CSN2) and κ casein (CSN3) content in the supernatants were determined by ELISA; the relative expression abundance of Janus kinase and signal transducer and activator of transcription factor (JAK/STAT) signaling pathway-related genes were detected by quantitative real-time PCR (qRT-PCR); and after the cells were treated with JAK2 signal blocker AG490, qRT-PCR was performed to test the relative expression abundance of CSN2 and CSN3 mRNAs...
February 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/28108507/flt3-and-jak2-mutations-in-acute-myeloid-leukemia-promote-inter-chromosomal-homologous-recombination-and-the-potential-for-copy-neutral-loss-of-heterozygosity-cn-loh
#2
Terry J Gaymes, Azim Mohamedali, Anthony Eiliazadeh, David Darling, Ghulam J Mufti
Acquired copy neutral loss-of-heterozygosity (CN-LOH) is a frequent occurrence in myeloid malignancies and is often associated with resistance to standard therapeutic modalities and poor survival. Here we show that constitutive signaling driven by mutated FLT3 and JAK2 confers inter-chromosomal homologous recombination (iHR), a precedent for CN-LOH. Using a targeted recombination assay, we determined significant iHR activity in internal tandem duplication FLT3 (FLT3-ITD) and JAK2V617F mutated cells. Sister chromatid exchanges, a surrogate measure of iHR, was significantly elevated in primary FLT3-ITD normal karyotype acute myeloid leukemia (NK-AML) compared to wild type FLT3 NK-AML...
January 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28103508/the-mechanism-of-alopolysaccharide-protecting-ulceralive-colitis
#3
Hu Lin, Li Honglang, Li Weifeng, Chen Junmin, Yang Jiantao, Gu Junjing
The aim of this study is to explain the mechanism of alopolysaccharide protecting ulceralive colitis in cells and animal models. We divided this study into two parts: cell and animal research parts. In the cell research, HT-29 cells were divided into normal group, model group, aloe polysacchride group and positive drug group, the cell model was used by tumor necrosis factor- α (TNF-α) combine with LPS, detecting IL-6 concentration of difference groups by Elisa testing, Apoptosis of each group was detected by flow cytometry...
January 16, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28100771/janus-kinase-2-jak2-dissociates-hepatosteatosis-from-hepatocellular-carcinoma-in-mice
#4
Sally Yu Shi, Stephanie A Schroer, Cynthia T Luk, Min Jeong Kim, David W Dodington, Lauren Lin, Tharini Sivasubramaniyam, Erica P Cai, Shun-Yan Lu, Kay-Uwe Wagner, Richard P Bazinet, Minna Woo
Hepatocellular carcinoma (HCC) is an end-stage complication of non-alcoholic fatty liver disease (NAFLD). Inflammation plays a critical role in the progression of non-alcoholic fatty liver disease and the development of hepatocellular carcinoma. However, whether steatosis per se promotes liver cancer and the molecular mechanisms that control the progression in this disease spectrum remain largely elusive. The Janus kinase-signal transducers and activators of transcription (JAK-STAT) pathway mediates signal transduction by numerous cytokines that regulate inflammation and may contribute to hepatocarcinogenesis...
January 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28100634/cryptochromes-regulate-igf-1-production-and-signaling-through-control-jak2-dependent-stat5b-phosphorylation
#5
Amol Chaudhari, Richa Gupta, Sonal Patel, Nikkhil Velingkaar, Roman Kondratov
Insulin like growth factor (IGF) signaling plays an important role in cell growth and proliferation and implicated in regulation of cancer, metabolism and aging. Here we report that IGF-1 level in blood and IGF-1 signaling demonstrates circadian rhythms. Circadian control occurs through Cryptochromes (CRYs), transcriptional repressors and components of the circadian clock. IGF-1 rhythms are disrupted in Cry deficient mice and IGF-1 level is reduced by 80% in these mice, which leads to reduced IGF signaling...
January 18, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28096537/jak2-v617f-activates-%C3%AE-1-integrin-mediated-adhesion-of-granulocytes-to-vascular-cell-adhesion-molecule-1-vcam1
#6
N Gupta, B Edelmann, T M Schnoeder, F C Saalfeld, D Wolleschak, S Kliche, B Schraven, F H Heidel, T Fischer
Leukemia accepted article preview online, 18 January 2017. doi:10.1038/leu.2017.26.
January 18, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28094778/adipocyte-fatty-acid-binding-protein-potentiates-toxic-lipids-induced-endoplasmic-reticulum-stress-in-macrophages-via-inhibition-of-janus-kinase-2-dependent-autophagy
#7
Ruby L C Hoo, Lingling Shu, Kenneth K Y Cheng, Xiaoping Wu, Boya Liao, Donghai Wu, Zhiguang Zhou, Aimin Xu
Lipotoxicity is implicated in the pathogenesis of obesity-related inflammatory complications by promoting macrophage infiltration and activation. Endoplasmic reticulum (ER) stress and adipocyte fatty acid binding protein (A-FABP) play key roles in obesity and mediate inflammatory activity through similar signaling pathways. However, little is known about their interplay in lipid-induced inflammatory responses. Here, we showed that prolonged treatment of palmitic acid (PA) increased ER stress and expression of A-FABP, which was accompanied by reduced autophagic flux in macrophages...
January 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28094236/deficiency-of-ptp1b-attenuates-hypothalamic-inflammation-via-activation-of-the-jak2-stat3-pathway-in-microglia
#8
Taku Tsunekawa, Ryoichi Banno, Akira Mizoguchi, Mariko Sugiyama, Takashi Tominaga, Takeshi Onoue, Daisuke Hagiwara, Yoshihiro Ito, Shintaro Iwama, Motomitsu Goto, Hidetaka Suga, Yoshihisa Sugimura, Hiroshi Arima
Protein tyrosine phosphatase 1B (PTP1B) regulates leptin signaling in hypothalamic neurons via the JAK2-STAT3 pathway. PTP1B has also been implicated in the regulation of inflammation in the periphery. However, the role of PTP1B in hypothalamic inflammation, which is induced by a high-fat diet (HFD), remains to be elucidated. Here, we showed that STAT3 phosphorylation (p-STAT3) was increased in microglia in the hypothalamic arcuate nucleus of PTP1B knock-out mice (KO) on a HFD, accompanied by decreased Tnf and increased Il10 mRNA expression in the hypothalamus compared to wild-type mice (WT)...
January 9, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28089238/ruxolitinib-for-symptom-control-in-patients-with-chronic-lymphocytic-leukaemia-a-single-group-phase-2-trial
#9
Preetesh Jain, Michael Keating, Sarah Renner, Charles Cleeland, Huang Xuelin, Graciela Nogueras Gonzalez, David Harris, Ping Li, Zhiming Liu, Ivo Veletic, Uri Rozovski, Nitin Jain, Phillip Thompson, Prithviraj Bose, Courtney DiNardo, Alessandra Ferrajoli, Susan O'Brien, Jan Burger, William Wierda, Srdan Verstovsek, Hagop Kantarjian, Zeev Estrov
BACKGROUND: Disease-related symptoms impair the quality of life of patients with chronic lymphocytic leukaemia (CLL) who do not require systemic therapy. Available therapies are not specifically aimed at symptom control. Because stimulation of the B-cell receptor activates JAK2 in CLL cells and the JAK2 inhibitor ruxolitinib improves symptoms in patients with myelofibrosis, we postulated that ruxolitinib would improve disease-related symptoms in patients with CLL. We did a phase 2 trial of ruxolitinib to test this hypothesis...
January 11, 2017: Lancet Haematology
https://www.readbyqxmd.com/read/28087906/-effect-and-its-molecular-mechanisms-of-curcumin-on-pulmonary-artery-smooth-muscle-cells-in-rat-model-with-chronic-obstructive-pulmonary-disease
#10
Xiangang Lin, Yenong Chen, Zhuqing Liu
Objective: To investigate the effects and the underlying molecular mechanisms of curcumin on pulmonary artery smooth muscle cells in rat model with chronic obstructive pulmonary disease (COPD). Methods: A total of 75 male Wistar rats were randomly divided into control group (group CN), model group (group M), low-dose curcumin group (group CL), medium-dose curcumin group (group CM) and high-dose curcumin group (group CH). HE staining was used to observe the morphology of pulmonary artery. Proliferating cell nuclear antigen (PCNA), apoptosis-related protein Bcl-2 and Bax were detected by immunohistochemical staining...
May 25, 2016: Zhejiang da Xue Xue Bao. Yi Xue Ban, Journal of Zhejiang University. Medical Sciences
https://www.readbyqxmd.com/read/28087904/-protective-effect-of-diosgenin-on-chondrocytes-mediated-by-jak2-stat3-signaling-pathway-in-mice-with-osteoarthritis
#11
Jun Liu, Xiaole He, Ping Zhen, Shenghu Zhou, Xusheng Li
Objective: To investigate the effect of diosgenin (Dgn) on chondrocytes and its relation to JAK2/STAT3 signaling pathway in mice with osteoarthritis (OA).Methods: Fifteen male C57BL/6 mice were randomly divided into three groups:control group, OA group and OA+Dgn group. After 4 weeks of treatment, the histopathological changes of cartilage tissue were observed by toluidine blue staining under light microscopy and the ultrastructure of chondrocytes was observed under electron microscopy. The primarily cultured chondrocytes of OA mice were randomly divided into 4 groups:(1) OA group, (2) Dgn group, (3) Dgn+AG490 group, (4) AG490 group...
May 25, 2016: Zhejiang da Xue Xue Bao. Yi Xue Ban, Journal of Zhejiang University. Medical Sciences
https://www.readbyqxmd.com/read/28087469/tofacitinib-ameliorates-inflammation-in-a-rat-model-of-airway-neutrophilia-induced-by-inhaled-lps
#12
Elena Calama, Isabel Ramis, Anna Domènech, Cristina Carreño, Jorge De Alba, Neus Prats, Montserrat Miralpeix
BACKGROUND: and purpose: The Janus Kinase (JAK) family mediates the cytokine receptor-induced signalling pathways involved in inflammatory processes. The activation of the signal transducers and activators of transcription (STATs) by JAK kinases is a key point in these pathways. Four JAK proteins, JAK1, JAK2, JAK3 and tyrosine kinase 2 (Tyk2) associate with the intracellular domains of surface cytokine receptors are phosphorylating STATs and modulating gene expression. The aim of this study was to explore the role of JAK inhibition in an acute model of inhaled lipopolysaccharide (LPS)-induced airway inflammation in rats through evaluating the effects of tofacitinib, a marketed pan-JAK inhibitor...
January 10, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28077684/targeting-aurora-kinase-a-and-jak2-prevents-gvhd-while-maintaining-treg-and-antitumor-ctl-function
#13
Brian C Betts, Anandharaman Veerapathran, Joseph Pidala, Hua Yang, Pedro Horna, Kelly Walton, Christopher L Cubitt, Steven Gunawan, Harshani R Lawrence, Nicholas J Lawrence, Said M Sebti, Claudio Anasetti
Graft-versus-host disease (GVHD) is a leading cause of nonrelapse mortality after allogeneic hematopoietic cell transplantation. T cell costimulation by CD28 contributes to GVHD, but prevention is incomplete when targeting CD28, downstream mammalian target of rapamycin (mTOR), or Aurora A. Likewise, interleukin-6 (IL-6)-mediated Janus kinase 2 (JAK2) signaling promotes alloreactivity, yet JAK2 inhibition does not eliminate GVHD. We provide evidence that blocking Aurora A and JAK2 in human T cells is synergistic in vitro, prevents xenogeneic GVHD, and maintains antitumor responses by cytotoxic T lymphocytes (CTLs)...
January 11, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28074070/gain-of-function-in-jak2-v617f-positive-t-cells
#14
G Nishanth, D Wolleschak, C Fahldieck, T Fischer, A Mullally, F Perner, T M Schnöder, S Just, F H Heidel, D Schlüter
Leukemia accepted article preview online, 11 January 2017. doi:10.1038/leu.2017.6.
January 11, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28068414/antibody-array-revealed-prl-3-affects-protein-phosphorylation-and-cytokine-secretion
#15
Yongyong Yang, Shenyi Lian, Lin Meng, Like Qu, Chengchao Shou
Phosphatase of regenerating liver 3 (PRL-3) promotes cancer metastasis and progression via increasing cell motility and invasiveness, however the mechanism is still not fully understood. Previous reports showed that PRL-3 increases the phosphorylation of many important proteins and suspected that PRL-3-enhanced protein phosphorylation may be due to its regulation on cytokines. To investigate PRL-3's impact on protein phosphorylation and cytokine secretion, we performed antibody arrays against protein phosphorylation and cytokines separately...
2017: PloS One
https://www.readbyqxmd.com/read/28068330/loss-of-p53-induces-leukemic-transformation-in-a-murine-model-of-jak2-v617f-driven-polycythemia-vera
#16
T Tsuruta-Kishino, J Koya, K Kataoka, K Narukawa, Y Sumitomo, H Kobayashi, T Sato, M Kurokawa
As leukemic transformation of myeloproliferative neoplasms (MPNs) worsens the clinical outcome, reducing the inherent risk of the critical event in MPN cases could be beneficial. Among genetic alterations concerning the transformation, the frequent one is TP53 mutation. Here we show that retroviral overexpression of Jak2 V617F mutant into wild-type p53 murine bone marrow cells induced polycythemia vera (PV) in the recipient mice, whereas Jak2 V617F-transduced p53-null mice developed lethal leukemia after the preceding PV phase...
January 9, 2017: Oncogene
https://www.readbyqxmd.com/read/28063793/interleukin-6-increases-the-expression-of-key-proteins-associated-with-steroidogenesis-in-human-nci-h295r-adrenocortical-cells
#17
Janae Strickland, Stephen McIlmoil, Brice J Williams, Dennis C Seager, James P Porter, Allan M Judd
Mechanisms of interleukin-6 (IL-6)-induced cortisol release (CR) were investigated by exposing H295R cells to IL-6 and determining mRNA/protein expression (PCR/western blots) for steroidogenic enzymes (SE), steroidogenic acute regulatory protein (StAR), steroidogenic factor-1 (SF-1)(enhances SE/StAR expression), activator protein 1 (AP-1)(regulates SE/StAR expression) and adrenal hypoplasia congenita-like protein (DAX-1)(inhibits SE/StAR expression). Promoter activity of StAR (SPA) was measured by a luciferase-coupled promoter...
January 4, 2017: Steroids
https://www.readbyqxmd.com/read/28057939/activating-jak2-mutants-reveal-cytokine-receptor-coupling-differences-that-impact-outcomes-in-myeloproliferative-neoplasm
#18
H Yao, Y Ma, Z Hong, L Zhao, S A Monaghan, M-C Hu, Lj-S Huang
Janus tyrosine kinase 2 (JAK2) mediates downstream signaling of cytokine receptors in all hematological lineages, yet constitutively active JAK2 mutants are able to drive selective expansion of particular lineage(s) in myeloproliferative neoplasm (MPN). The molecular basis of lineage specificity is unclear. Here we show that three activating JAK2 mutants with similar kinase activities in vitro elicit distinctive MPN phenotypes in mice by differentially expanding erythroid vs. granulocytic precursors. Molecularly, this reflects the differential binding of JAK2 mutants to cytokine receptors EpoR and GCSFR in the erythroid vs granulocytic lineage and the creation of unique receptor/JAK2 complexes that generate qualitatively distinct downstream signals...
January 6, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28057739/aberrant-let7a-hmga2-signaling-activity-with-unique-clinical-phenotype-in-jak2-mutated-myeloproliferative-neoplasms
#19
Chih-Cheng Chen, Jie-Yu You, Jrhau Lung, Cih-En Huang, Yi-Yang Chen, Yu-Wei Leu, Hsing-Ying Ho, Chian-Pei Li, Chang-Hsien Lu, Kuan-Der Lee, Chia-Chen Hsu, Jyh-Pyng Gau
High mobility group AT-hook 2 (HMGA2) is an architectural transcriptional factor that is negatively regulated by Let-7 microRNA through binding to its 3-untranslated region (3-UTR). Transgenic mice expressing HMGA2 with a truncation of its 3-UTR has been shown to exhibit a myeloproliferative phenotype. To decipher the Let-7-HMGA2 axis in myeloproliferative neoplasms (MPN), we employed an in vitro model supplemented with clinical correlation. Ba/F3 cells with inducible JAK2V617F expression (Ton.JAK2.V617F cells) showed up-regulation of HMGA2 with concurrent let-7a repression...
January 5, 2017: Haematologica
https://www.readbyqxmd.com/read/28056804/indelseek-detection-of-complex-insertions-and-deletions-from-next-generation-sequencing-data
#20
Chun Hang Au, Anskar Y H Leung, Ava Kwong, Tsun Leung Chan, Edmond S K Ma
BACKGROUND: Complex insertions and deletions (indels) from next-generation sequencing (NGS) data were prone to escape detection by currently available variant callers as shown by large-scale human genomics studies. Somatic and germline complex indels in key disease driver genes could be missed in NGS-based genomics studies. RESULTS: INDELseek is an open-source complex indel caller designed for NGS data of random fragments and PCR amplicons. The key differentiating factor of INDELseek is that each NGS read alignment was examined as a whole instead of "pileup" of each reference position across multiple alignments...
January 5, 2017: BMC Genomics
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