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https://www.readbyqxmd.com/read/28748356/pd-l1-induced-by-ifn-%C3%AE-from-tumor-associated-macrophages-via-the-jak-stat3-and-pi3k-akt-signaling-pathways-promoted-progression-of-lung-cancer
#1
Xiaohui Zhang, Yuanyuan Zeng, Qiuxia Qu, Jianjie Zhu, Zeyi Liu, Weiwei Ning, Hui Zeng, Nan Zhang, Wenwen Du, Cheng Chen, Jian-An Huang
BACKGROUND: Interferon-γ (IFN-γ) is conventionally regarded as an inflammatory cytokine that has a pivotal role in anti-infection and tumor immune surveillance. It has been used clinically to treat a variety of malignancies. However, increased evidence has suggested IFN-γ can act to induce tumor progression. The role of IFN-γ in regulating antitumor immunity appears to be complex and paradoxical. The mechanism underlying the dual aspects of IFN-γ function in antitumor immunity is not clear...
July 26, 2017: International Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28745314/a-muscle-specific-protein-myoferlin-modulates-il-6-stat3-signaling-by-chaperoning-activated-stat3-to-nucleus
#2
A Yadav, B Kumar, J C Lang, T N Teknos, P Kumar
Myoferlin, a member of ferlin family of proteins, was first discovered as a candidate gene for muscular dystrophy and cardiomyopathy. Recently, myoferlin was shown to be also expressed in endothelial and cancer cells where it was shown to modulate vascular endothelial growth factor (VEGFR)-2 and epidermal growth factor receptor (EGFR) signaling by enhancing their stability and recycling. Based on these reports, we hypothesized that myoferlin might be regulating IL-6 signaling by modulating IL-6R stabilization and recycling...
July 24, 2017: Oncogene
https://www.readbyqxmd.com/read/28744013/the-t-cell-leukemia-associated-ribosomal-rpl10-r98s-mutation-enhances-jak-stat-signaling
#3
T Girardi, S Vereecke, S O Sulima, Y Khan, L Fancello, J W Briggs, C Schwab, J O de Beeck, J Verbeeck, J Royaert, E Geerdens, C Vicente, S Bornschein, C J Harrison, J P Meijerink, J Cools, J D Dinman, K R Kampen, K De Keersmaecker
Several somatic ribosome defects have recently been discovered in cancer, yet their oncogenic mechanisms remain poorly understood. Here we investigated the pathogenic role of the recurrent R98S mutation in ribosomal protein L10 (RPL10-R98S) found in T-ALL. The JAK-STAT signaling pathway is a critical controller of cellular proliferation and survival. A proteome screen revealed overexpression of several Jak-Stat signaling proteins in engineered RPL10-R98S mouse lymphoid cells, which we confirmed in hematopoietic cells from transgenic Rpl10-R98S mice and T-ALL xenograft samples...
July 24, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28743877/chronic-activation-of-jnk-jak-stat-and-oxidative-stress-signalling-causes-the-loser-cell-status
#4
Iwo Kucinski, Michael Dinan, Golnar Kolahgar, Eugenia Piddini
Cell competition is a form of cell interaction that causes the elimination of less fit cells, or losers, by wild-type (WT) cells, influencing overall tissue health. Several mutations can cause cells to become losers; however, it is not known how. Here we show that Drosophila wing disc cells carrying functionally unrelated loser mutations (Minute and mahjong) display the common activation of multiple stress signalling pathways before cell competition and find that these pathways collectively account for the loser status...
July 26, 2017: Nature Communications
https://www.readbyqxmd.com/read/28743868/virus-and-dsrna-triggered-transcriptional-responses-reveal-key-components-of-honey-bee-antiviral-defense
#5
Laura M Brutscher, Katie F Daughenbaugh, Michelle L Flenniken
Recent high annual losses of honey bee colonies are associated with many factors, including RNA virus infections. Honey bee antiviral responses include RNA interference and immune pathway activation, but their relative roles in antiviral defense are not well understood. To better characterize the mechanism(s) of honey bee antiviral defense, bees were infected with a model virus in the presence or absence of dsRNA, a virus associated molecular pattern. Regardless of sequence specificity, dsRNA reduced virus abundance...
July 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28742984/single-versus-combined-immunoregulatory-approach-using-pd-1-and-ctla-4-modulators-in-controlling-sepsis
#6
Courtney P Rudick, David L Cornell, Devendra K Agrawal
Sepsis is a disease process characterized by an extreme inflammatory response followed by a period of severe immunosuppression. In recent years, there has been improved survival in the initial immune response during systemic inflammatory response syndrome, and compensatory anti-inflammatory response, yet is mostly unchanged with 18-30% mortality during the later stage of sepsis despite numerous Phase 3 clinical trials. Areas covered: This review article presents a critical evaluation of the most promising newer studies aimed at improving the immunosuppressive stage of sepsis...
July 25, 2017: Expert Review of Clinical Immunology
https://www.readbyqxmd.com/read/28742217/the-inflammatory-cytokine-interferon-gamma-inhibits-sortilin-1-expression-in-hepatocytes-via-the-jak-stat-pathway
#7
John Pirault, Konstantinos A Polyzos, Marcelo H Petri, Daniel Fj Ketelhuth, Magnus Bäck, Göran K Hansson
Sortilin-1, a receptor of the VPS10p family, has been associated with cardiovascular disease in genome-wide association studies. It is implicated in lipoprotein metabolism, secretion of proprotein convertase subtilisin/kexin type 9 (PCSK9) and secretion of inflammatory cytokines. However, its own regulation remains unclear. Chronic inflammation is a hallmark of atherosclerosis and absence of regulatory T (Treg) cells is associated with reduced protein expression of sortilin-1 in the liver. Therefore, we postulated that mediator(s) of inflammation known to be downregulated by regulatory T cells may modulate sortilin-1 expression...
July 25, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28742207/socs3-overexpression-enhances-adm-resistance-in-bladder-cancer-t24-cells
#8
M-Z Li, D-H Lai, H-B Zhao, Z Chen, Q-X Huang, J Situ
OBJECTIVE: JAK-STAT3 signaling pathway widely participates in cell proliferation and apoptosis. Suppressor of cytokine signaling 3 (SOCS3) is a negative regulator of JAK-STAT3. SOCS3 downregulation is associated with drug resistance in breast cancer and leukemia. However, its role in bladder cancer drug resistance is still unclear. This study established ADM resistant bladder cancer cell model to investigate the role of SOCS3-JAK/STAT3 signaling pathway ADM resistance. MATERIALS AND METHODS: ADM drug resistant cell line T24/ADM was established...
July 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28741594/polar-phase-transitions-in-heteroepitaxial-stabilized-la-sub-0-5-sub-y-sub-0-5-sub-alo-sub-3-sub-thin-films
#9
Shenghua Liu, Chunfeng Zhang, Mengya Zhu, Qian He, Jak Chakhalian, Xiaoran Liu, Albina Borisevich, Xiaoyong Wang, Min Xiao
We report on the fabrication of epitaxial La0.5Y0.5AlO3 ultrathin films on (001) LaAlO3 substrates. Structural characterizations by scanning transmission electron microscopy and X-ray diffraction confirm the high quality of the film with AlO6 octahedral tilt pattern. Unlike either of the nonpolar parent compound, LaAlO3 and YAlO3, second harmonic generation measurements on the thin films suggest a nonpolar - polar phase transition at Tc near 500 K, and a polar - polar phase transition at Ta near 160 K. By fitting the angular dependence of the second harmonic intensities, we further propose that the two polar structures can be assigned to the Pmc21 and Pmn21 space group, while the high temperature nonpolar structure belongs to the Pbnm space group...
July 25, 2017: Journal of Physics. Condensed Matter: An Institute of Physics Journal
https://www.readbyqxmd.com/read/28739827/transcriptional-profiling-of-the-chicken-tracheal-response-to-virulent-mycoplasma-gallisepticum-strain-rlow
#10
J Beaudet, E R Tulman, K Pflaum, X Liao, G F Kutish, S M Szczepanek, L K Silbart, S J Geary
Mycoplasma gallisepticum, the primary etiologic agent of Chronic Respiratory Disease (CRD) in poultry, leads to prolonged recruitment and activation of inflammatory cells in the respiratory mucosa. This is consistent with the current model of immune dysregulation that ostensibly allows the organism to evade clearance mechanisms and establish chronic infection. To date, studies using qRT-PCR and microarrays have shown a significant transient up-regulation of cytokines and chemokines from tracheal epithelial cells (TECs) in vitro and tracheal tissue ex vivo in response to virulent strain Rlow, that contributes to the infiltration of inflammatory cells into the tracheal mucosa...
July 24, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28739485/hsp90-is-necessary-for-the-ack1-dependent-phosphorylation-of-stat1-and-stat3
#11
Nisintha Mahendrarajah, Marina E Borisova, Sigrid Reichardt, Maren Godmann, Andreas Sellmer, Siavosh Mahboobi, Andrea Haitel, Katharina Schmid, Lukas Kenner, Thorsten Heinzel, Petra Beli, Oliver H Krämer
Signal transducers and activators of transcription (STATs) are latent, cytoplasmic transcription factors. Janus kinases (JAKs) and activated CDC42-associated kinase-1 (ACK1/TNK2) catalyse the phosphorylation of STAT1 and the expression of its target genes. Here we demonstrate that catalytically active ACK1 promotes the phosphorylation and nuclear accumulation of STAT1 in transformed kidney cells. These processes are associated with STAT1-dependent gene expression and an interaction between endogenous STAT1 and ACK1...
July 21, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28739278/p38mapk-plays-a-critical-role-in-induction-of-a-pro-inflammatory-phenotype-of-retinal-m%C3%A3-ller-cells-following-zika-virus-infection
#12
Shuang Zhu, Huanle Luo, Hua Liu, Yonju Ha, Elizabeth R Mays, Ryan E Lawrence, Evandro Winkelmann, Alan D Barrett, Sylvia B Smith, Min Wang, Tian Wang, Wenbo Zhang
Zika virus (ZIKV) infection has been associated with ocular abnormalities such as chorioretinal atrophy, optic nerve abnormalities, posterior uveitis and idiopathic maculopathy. Yet our knowledge about ZIKV infection in retinal cells and its potential contribution to retinal pathology is still very limited. Here we found that primary Müller cells, the principal glial cells in the retina, expressed a high level of ZIKV entry cofactor AXL gene and were highly permissive to ZIKV infection. In addition, ZIKV-infected Müller cells exhibited a pro-inflammatory phenotype and produced many inflammatory and growth factors...
July 21, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28739255/wp1066-a-small-molecule-inhibitor-of-the-jak-stat3-pathway-inhibits-ceramide-glucosyltransferase-activity
#13
Hirotaka Tsurumaki, Hikaru Katano, Kousuke Sato, Ryu Imai, Satomi Niino, Yoshio Hirabayashi, Shinichi Ichikawa
WP1066 is a well-known inhibitor of the JAK/STAT3 signaling pathway. By a screen of known small molecule inhibitors of various enzymes and protein factors, we identified WP1066 as a ceramide glucosyltransferase inhibitor. Ceramide glucosyltransferase catalyzes the first glycosylation step during glycosphingolipid synthesis. We found that WP1066 inhibited the activity of ceramide glucosyltransferase with an IC50 of 7.2 μM, and that its action was independent of JAK/STAT3 pathway blockade. Moreover, the modes of inhibition of ceramide glucosyltransferase were uncompetitive with respect to both C6-NBD-cermide and UDP-glucose...
July 21, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28738804/oncogenic-long-noncoding-rna-landscape-in-breast-cancer
#14
Shouping Xu, Dejia Kong, Qianlin Chen, Yanyan Ping, Da Pang
BACKGROUND: Few long noncoding RNAs (lncRNAs) that act as oncogenic genes in breast cancer have been identified. METHODS: Oncogenic lncRNAs associated with tumourigenesis and worse survival outcomes were examined and validated in Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA), respectively. Then, the potential biological functions and expression regulation of these lncRNAs were studied via bioinformatics and genome data analysis. Moreover, progressive breast cancer subtype-specific lncRNAs were investigated via high-throughput sequencing in our cohort and TCGA validation...
July 24, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28737134/nephrotic-syndrome-in-primary-myelofibrosis-with-renal-extramedullary-hematopoiesis-and-glomerulopathy-in-the-jak-inhibitor-era
#15
Rachele Del Sordo, Rachele Brugnano, Carla Covarelli, Gioia Fiorucci, Franca Falzetti, Giorgio Barbatelli, Emidio Nunzi, Angelo Sidoni
Primary myelofibrosis (PMF) is an uncommon form of myeloproliferative neoplasm (MPN) characterized by a proliferation of predominantly megakaryocytes and granulocytes in the bone marrow that, in fully-developed disease, is associated with reactive deposition of fibrous connective tissue, extramedullary hematopoiesis (EMH), and splenomegaly. Kidney involvement is rare and clinically presents with proteinuria, nephrotic syndrome, and renal insufficiency. Renal damage can be due to EMH and glomerulopathy. Renal EMH presents three patterns: infiltration of the interstitium with possible renal failure caused by functional damage of parenchyma and vessels, infiltration of capsule and pericapsular adipose tissue, and sclerosing mass-like lesions that can cause hydronephrosis and hydroureter with obstructive uropathy and renal failure...
July 24, 2017: Clinical Nephrology
https://www.readbyqxmd.com/read/28733465/the-retinol-binding-protein-receptor-stra6-regulates-diurnal-insulin-responses
#16
Christy M Gliniak, J Mark Brown, Noa Noy
It has long been appreciated that insulin action is closely tied to circadian rhythms. However, mechanisms that dictate diurnal insulin sensitivity in metabolic tissues are not well understood. Retinol binding protein 4 (RBP4) has been implicated as a driver of insulin resistance in rodents and humans, and has become an attractive drug target in type 2 diabetes. RBP4 is synthesized primarily in the liver where it binds retinol and transports it to tissues throughout the body. The retinol-RBP4 complex (holo-RBP) can be recognized by a cell surface receptor known as stimulated by retinoic acid 6 (STRA6) which transports retinol into cells...
July 21, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28732559/socs-1-is-involved-in-tnf-%C3%AE-induced-mitochondrial-dysfunction-and-apoptosis-in-renal-tubular-epithelial-cells
#17
Chunyang Du, Fang Yao, Yunzhuo Ren, Yunxia Du, Jinying Wei, Haijiang Wu, Huijun Duan, Yonghong Shi
Tumor necrosis factor-α (TNF-α) is suggested to induce mitochondrial dysfunction and apoptosis of renal tubular epithelial cells that possibly exacerbates renal function in chronic kidney disease (CKD). Here we investigated whether suppressor of cytokine signaling-1 (SOCS-1), an inhibitor of cytokine signaling, was involved in TNF-α-induced human renal tubular epithelial cells (HKCs) oxidative stress and apoptosis. TNF-α promoted the protein and mRNA expression of SOCS-1 in a time and dose dependent manner, along with increased cell apoptosis and activation of apoptosis signal regulating kinase-1(ASK1) in HKCs...
June 30, 2017: Tissue & Cell
https://www.readbyqxmd.com/read/28732065/direct-targets-of-pstat5-signalling-in-erythropoiesis
#18
Kevin R Gillinder, Hugh Tuckey, Charles C Bell, Graham W Magor, Stephen Huang, Melissa D Ilsley, Andrew C Perkins
Erythropoietin (EPO) acts through the dimeric erythropoietin receptor to stimulate proliferation, survival, differentiation and enucleation of erythroid progenitor cells. We undertook two complimentary approaches to find EPO-dependent pSTAT5 target genes in murine erythroid cells: RNA-seq of newly transcribed (4sU-labelled) RNA, and ChIP-seq for pSTAT5 30 minutes after EPO stimulation. We found 302 pSTAT5-occupied sites: ~15% of these reside in promoters while the rest reside within intronic enhancers or intergenic regions, some >100kb from the nearest TSS...
2017: PloS One
https://www.readbyqxmd.com/read/28729093/pim-kinases-1-2-and-3-in-intracellular-lif-signalling-proliferation-and-apoptosis-in-trophoblastic-cells
#19
Stella Mary Photini, Wittaya Chaiwangyen, Maja Weber, Boodor Al-Kawlani, Rodolfo R Favaro, Udo Jeschke, Ekkehard Schleussner, Diana M Morales-Prieto, Udo R Markert
Proviral insertion in murine (PIM) lymphoma proteins are mainly regulated by the Janus Kinase/Signal Transducer Activator of Transcription (JAK/STAT) signaling pathway, which can be activated by members of the Interleukin-6 (IL-6) family, including Leukemia Inhibitory Factor (LIF). Aim of the study was to compare PIM1, PIM2 and PIM3 expression and potential cellular functions in human first and third trimester trophoblast cells, the immortalized first trimester extravillous trophoblast cell line HTR8/SVneo and the choriocarcinoma cell line JEG-3...
July 17, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28728978/anticancer-drug-loaded-quantum-dots-engineered-polymeric-nanoparticles-diagnosis-therapy-combined-approach
#20
D Belletti, G Riva, M Luppi, G Tosi, F Forni, M A Vandelli, B Ruozi, F Pederzoli
Primary Effusion Lymphoma (PEL) is an HHV-8-related non Hodgkin lymphoma localized in body cavities (as pleural, peritoneal and pericardial) presenting lymphomatous effusion that, until now, lack of an effective therapy. Curcumin was reported to display pro-apoptotic effect via the inhibition of the JAK/STAT pathway, that is overexpressed in PEL cells, as consequence of virus infection. The administration of curcumin is severely restricted by its physicochemical properties, mainly its low solubility in biological fluid and consequently low bioavailability...
July 18, 2017: European Journal of Pharmaceutical Sciences
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